Water → HCID 10141175, compound

HRID 1058786Notes

Reaction equation

HRID 1058786 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

5

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydrideHCID 22506638(-)-1-[(4-Chlorophenyl)(4-formylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

Product 1

HCID 10141175HCID 10141175, compoundYield 57.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

0.020 g of sodium borohydride is added to a solution of 0.50 g of (RS)-1-{(4-chlorophenyl)-(4-formylphenyl)methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine in 15 cm3 of methanol at 0° C. After 1 hour at 0° C., 40 cm3 of water are added and the product extracted with 100 cm3 of dichloromethane. The organic phase is washed twice with 40 cm3 of water and then 40 cm3 of a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3.2 cm, height 14 cm), at an argon pressure of 0.5 bar with a mixture of ethyl acetate and cyclohexane (30/70 by volume) and collecting 20 cm3 fractions. Fractions 20 to 25 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.29 g of (RS)-1-{(4-chlorophenyl)[4-(hydroxymethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine is obtained in the form of a white foam [NMR spectrum in DMSO-d6, T=300K, δ in ppm (250 MHz): 3.02 (3H, s, SCH3), 3.90 (2H, s, NCH2), 4.20 (2H, s, NCH2), 4.42 (2H, d, J=5 Hz, OCH2), 4.75 (1H, s, NCH), 5.10 (1H, t, J=5 Hz, OH), between 7.10 and 7.50 (11H, m, 11CH arom.)].

Workup

  1. extractionthe product extracted with 100 cm3 of dichloromethane
  2. washThe organic phase is washed twice with 40 cm3 of water
  3. dry with material40 cm3 of a saturated sodium chloride solution, dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue obtained
  7. customis chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 3.2 cm, height 14 cm), at an argon pressure of 0.5 bar with a mixture of ethyl acetate and cyclohexane (30/70 by volume)
  8. customcollecting 20 cm3 fractions
  9. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-35025fbe48584424b239a7bbca3b4db6
Source dataset
uspto-grants-2003_02
Patent number
US06518264B2

Reaction notes

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