Monofluorocyclopropane compound and its preparation method and application
A compound and alkyl technology, applied in the field of monofluorocyclopropane compounds and their preparation, can solve the problems of low conversion rate, poor enantioselectivity and diastereoselectivity, poor substrate universality and the like
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
preparation example Construction
[0134] The preparation method of formula I compound
[0135] The preparation method of the compound of formula I provided by the invention comprises steps:
[0136] (a1) reacting the compound of formula IV with a fluorinating reagent to obtain the compound of formula II;
[0137] Or (a2) the compound of formula VI is reacted with an alkylating agent to obtain the compound of formula II;
[0138]
[0139] (b) reacting a compound of formula III with a compound of formula II in an organic solvent and in the presence of a base to form the compound of formula I,
[0140]
[0141] In various forms, R 1 , R 2 , Ra, Rb, R 4 is defined as above;
[0142] In another preferred example, the fluorinating reagent can be a fluorinating reagent commonly used in the art, for example, the fluorinating reagent includes but is not limited to: NFSI fluorinating agent, Selectfluor fluorinating agent, NFTh fluorinating agent, NFOBS fluorinating agent fluorinating agent, nitrogen-fluoro...
Embodiment 1
[0184] Synthesis of [(R)-N-p-toluenesulfonyl]monofluoromethylphenylsulfoximine ((R)-N-Tosyl-S-monofluoromethyl-S-phenylsulfoximine)
[0185]
[0186] Under nitrogen protection, 9.3 g (30 mmol) of [(S)-N-p-toluenesulfonyl] methylphenyl sulfoximine and 150 ml of dry THF were added to a 250 ml three-necked flask, cooled to -78 °C, and then Add n-butyllithium nBuLi (1.6M, 33mmol, 1.1 equiv) dropwise, keep the reaction at -78°C for half an hour, then add NFSI (12g, 1.2 equiv). Naturally heated to 25°C and stirred overnight, then added H 2 O quenched the reaction and extracted with ether to obtain an organic layer. The organic layer was washed with saturated brine, MgSO was added 4 After drying, the solvent was evaporated, and the product was obtained by column chromatography (6.4 g, yield 65%).
[0187] white solid. Melting point: 89~91℃. Optical rotation: [α] D 24 =+49.8° (c=1.00, CHCl 3 ). Enantiomeric excess is determined by chiral column Lux 5u Amylose-2 (4.6mm×250mm...
Embodiment 2
[0190] Synthesis of [(R)-N-p-toluenesulfonyl]-1-fluoroethylphenylsulfoximine ((R)-N-Tosyl-S-1-fluoroethy-S-phenylsulfoximine)
[0191]
[0192] Under nitrogen protection, 1.96 g (6 mmol) of [(R)-N-p-toluenesulfonyl] fluoromethylphenyl sulfoximine and 30 ml of dry THF were added to a 50 ml three-necked flask, cooled to -78°C, Then nBuLi (1.6M, 6.6mmol, 1.1 equiv) was added dropwise, and after the reaction was kept at -78°C for half an hour, MeI (2.13g, 2.5 equiv) was added. After reacting at -78°C for 1 hour, the temperature was naturally raised to 25°C and stirred overnight, and then H 2 O quenched the reaction and extracted with ether to obtain an organic layer. The organic layer was washed with saturated brine, MgSO was added 4 After drying, the solvent was evaporated, and the product was obtained by column chromatography (1.54 g, yield 75%). One of the diastereomer data:
[0193] white solid. Melting point: 117-118℃. Optical rotation: [α] D 28 =+141.7° (c=0.52, CH...
PUM
| Property | Measurement | Unit |
|---|---|---|
| melting point | aaaaa | aaaaa |
| melting point | aaaaa | aaaaa |
| melting point | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More