Water → HCID 10141175, compound

HRID 25192Notes

Reaction equation

[BH4-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:28]2[CH:33]=[CH:32][C:31]([CH:34]=[O:35])=[CH:30][CH:29]=2)[N:11]2[CH2:14][C:13](=[C:15]([C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=3)[S:16]([CH3:19])(=[O:18])=[O:17])[CH2:12]2)=[CH:6][CH:5]=1.O>CO>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:28]2[CH:29]=[CH:30][C:31]([CH2:34][OH:35])=[CH:32][CH:33]=2)[N:11]2[CH2:12][C:13](=[C:15]([C:20]3[CH:21]=[C:22]([F:27])[CH:23]=[C:24]([F:26])[CH:25]=3)[S:16]([CH3:19])(=[O:18])=[O:17])[CH2:14]2)=[CH:6][CH:5]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 30 mg of sodium borohydride in 2 cm3 of methanol is poured into a solution of 0.77 g of (−)-1-[(4-chlorophenyl)(4-formylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine in 20 cm3 of methanol at 0° C. under argon. After stirring for 4 hours at 0° C., water is added and the mixture is then extracted with dichloromethane. The organic phase is washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then evaporated to dryness under reduced pressure (2.7 kpa). The white foam obtained is purified on a silica gel column (particle size 0.04-0.06 mm, diameter 3.2 cm, height 17 cm) with, as eluent, a cyclohexane/ethyl acetate (60/40 by volume) mixture. 0.1 g of (+)-1-[(4-chlorophenyl)(4-hydroxymethylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine is obtained, after crystallization from 1.5 cm3 of absolute ethanol, in the form of white crystals melting at 190° C., [a]20D=+4.2° (c=0.5% in methanol) [NMR spectrum in DMSO-d6, T=300K, δ in ppm (300 MHz): 3.05 (3H, s, SCH3), 3.95 (2H, s, NCH2), 4.22 (2H, s, NCH2), 4.48 (2H, d, J=6 Hz, CH2O), 4.75 (1H, s, NCH), 5.15 (1H, t, J=6 Hz, OH), 7.20 (2H, m, 2CH arom.), 7.28 (2H, d, J=7 Hz, 2CH arom.), 7.40(5H, m, 5 CH arom.), 7.50 (2H, d, J=7 Hz, 2CH arom.)].

Workup

extractionthe mixture is then extracted with dichloromethane
washThe organic phase is washed with a saturated aqueous sodium chloride solution
dry with materialdried over magnesium sulfate
customevaporated to dryness under reduced pressure (2.7 kpa)
customThe white foam obtained
customis purified on a silica gel column (particle size 0.04-0.06 mm, diameter 3.2 cm, height 17 cm) with, as eluent

Sources & evidence

ORD record: ord-9d0f7c9faeb94bf393dd2356d950d9b4
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06858603B2

Reaction notes

Loading…