Sodium borohydride → [(3S,4S,5R,6S)-3,4,5-tri-benzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-yl]methanol

HRID 1912995Notes

Reaction equation

HRID 1912995 reaction equation
[CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@:12]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[C:43]([F:49])[C:42]=3[F:50])[CH:34]=2)([O:31][CH3:32])[O:11][C@:10]1([CH2:53][OH:54])[CH:51]=[O:52])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>>[CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C@@:12]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[C:43]([F:49])[C:42]=3[F:50])[CH:34]=2)([O:31][CH3:32])[O:11][C:10]1([CH2:51][OH:52])[CH2:53][OH:54])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 4311764Sodium borohydrideHCID 86685113(2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehyde

Product 1

HCID 68015201[(3S,4S,5R,6S)-3,4,5-tri-benzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-yl]methanolYield 39.9%

Procedure

(2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehyde 2m (1.29 g, 1.71 mmol) was dissolved in 15 mL of mixed solution (THF and MeOH, v:v=1:2), followed by addition of sodium borohydride (129 mg, 3.42 mmol). The reaction mixture was stirred for 20 minutes. Thereafter, the reaction mixture was concentrated under reduced pressure and partitioned after 30 mL ethyl acetate and 15 mL saturated sodium chloride solution were added. The aqueous phase was extracted with ethyl acetate (15 mL×2) and the organic extract was combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica gel chromatography with elution system B to obtain the title compound [(3S,4S,5R,6S)-3,4,5-tri-benzyloxy-6-[4-chloro-3-[(2,3-difluoro-4-methoxy-phenyl)methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-yl]methanol 2n (520 mg, white solid), with yield: 40%.

Workup

  1. concentrationThereafter, the reaction mixture was concentrated under reduced pressure
  2. custompartitioned after 30 mL ethyl acetate and 15 mL saturated sodium chloride solution
  3. additionwere added
  4. extractionThe aqueous phase was extracted with ethyl acetate (15 mL×2)
  5. extractionthe organic extract
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe resulting residue was purified by silica gel chromatography with elution system B

Sources & evidence

ORD record
ord-7c68716de9594a85be743b7b423ca6cf
Source dataset
uspto-grants-2013_12
Patent number
US08609622B2

Reaction notes

Loading…