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

HRID 1055553Notes

Reaction equation

HRID 1055553 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][CH2:48][C:49]([F:52])([F:51])[F:50])=[CH:43][CH:42]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C@@:10]1([CH2:55][OH:56])[CH:53]=[O:54])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>CO>[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][CH2:48][C:49]([F:52])([F:51])[F:50])=[CH:45][CH:46]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C:10]1([CH2:55][OH:56])[CH2:53][OH:54])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 118378024(2R,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2,2-trifluoro ethoxy)phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehyde

Product 1

HCID 86685152[(3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-yl]methanolYield 56.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-5 °C

Procedure

To a solution of (2R,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-(2,2,2-trifluoroethoxyl) phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-carbaldehyde 17j (4.80 g, 6.04 mmol) in methanol (50 mL) was added sodium borohydride (326 mg, 8.62 mmol) at −5° C. The mixture was stirred for 30 min at −5° C. The reaction mixture was quenched with saturated aqueous ammonium chloride (15 mL) and concentrated in vacuo to remove most of the solvent. To the residue was added water (50 mL). The mixture was extracted with ethyl acetate (30 mL×3). The combined organic layers were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=10/1 to give the title compound 17k as light yellow oil (2.7 g, 56.3%, HPLC: 89.2%). This material was not further purified. The compound was characterized by the following spectroscopic data: 1H NMR (600 MHz, DMSO-d6) δ(ppm): 7.53 (d, 2H), 7.40 (d, 1H), 7.33 (d, 2H), 7.31-7.22 (m, 12H), 7.08-7.01 (m, 4H), 6.89 (d, 2H), 4.90 (s, 1H), 4.85-4.74 (m, 3H), 4.71-4.63 (m, 3H), 4.52 (d, 1H), 4.30 (s, 1H), 4.05 (m, 3H), 3.99-3.85 (m, 3H), 3.79 (m, 2H), 3.54 (d, 1H), 3.19 (d, 1H), 3.09 (s, 3H).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous ammonium chloride (15 mL)
  2. concentrationconcentrated in vacuo
  3. customto remove most of the solvent
  4. additionTo the residue was added water (50 mL)
  5. extractionThe mixture was extracted with ethyl acetate (30 mL×3)
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by silica gel chromatography
  10. washeluted with PE/EtOAc(v/v)=10/1

Sources & evidence

ORD record
ord-9ef054e8f1484f4abc7a50341e957902
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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