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

HRID 1913043Notes

Reaction equation

HRID 1913043 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][C:48]([F:51])([F:50])[F:49])=[CH:43][CH:42]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C@:10]1([CH2:54][OH:55])[CH:52]=[O:53])[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:18]=[CH:19][CH:20]=[CH:21][CH:22]=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:42]=[CH:43][C:44]([O:47][C:48]([F:51])([F:50])[F:49])=[CH:45][CH:46]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C:10]1([CH2:54][OH:55])[CH2:52][OH:53])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 4311764Sodium borohydrideHCID 86685142(2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydro-pyran-2-carbaldehyde

Product 1

HCID 86685143[(3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-yl]methanolYield 31.5%

Procedure

(2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehyde 6p (1.27 g, 1.63 mmol) was dissolved in 10 mL of mixed solution (THF and MeOH, v:v=1:1) and followed by addition of sodium borohydride (0.12 g, 3.26 mmol) in batch. The reaction mixture was stirred for 1.5 hours. Thereafter, the reaction mixture was concentrated under reduced pressure and was partitioned after 30 mL of ethyl acetate were added. The organic extract was washed with saturated sodium chloride solution (15 mL×2), 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 E to obtain the title compound [(3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(trifluoromethoxy)phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-yl]methanol 6q (400 mg, white solid), yield: 31.5%. 1H NMR (400 MHz, CD3OD): δ 7.58 (dd, 1H), 7.54 (d, 1H), 7.39 (d, 1H), 7.31-7.24 (m, 13H), 7.16 (d, 2H), 7.11-7.06 (m, 4H), 4.92 (d, 1H), 4.76 (d, 1H), 4.66-4.59 (m, 1H), 4.27-4.22 (m, 2H), 4.17-4.10 (m, 2H), 4.07-4.04 (m, 3H), 3.99-3.95 (m, 2H), 3.77 (d, 1H), 3.65-3.60 (m, 2H), 3.35 (s, 2H), 3.18 (s, 3H).

Workup

  1. concentrationThereafter, the reaction mixture was concentrated under reduced pressure
  2. customwas partitioned after 30 mL of ethyl acetate
  3. additionwere added
  4. extractionThe organic extract
  5. washwas washed with saturated sodium chloride solution (15 mL×2)
  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 E

Sources & evidence

ORD record
ord-706048ddb766431482f98aa5453b9a24
Source dataset
uspto-grants-2013_12
Patent number
US08609622B2

Reaction notes

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