Water → (3aS,5S,6R,6aS)-5-((S)-(3-(4-chlorobenzyl)-4-methylphenyl)(hydroxy)-methyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol

HRID 1499292Notes

Reaction equation

HRID 1499292 reaction equation
[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][C:7]2[CH:8]=[C:9]([C:14]([C@@H:16]3[O:25][C@H:19]4[O:20][C:21]([CH3:24])([CH3:23])[O:22][C@H:18]4[C@@H:17]3[OH:26])=[O:15])[CH:10]=[CH:11][C:12]=2[CH3:13])=[CH:4][CH:3]=1.O.[BH4-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[CH:8]=[C:9]([C@H:14]([OH:15])[C@@H:16]3[O:25][C@H:19]4[O:20][C:21]([CH3:24])([CH3:23])[O:22][C@H:18]4[C@@H:17]3[OH:26])[CH:10]=[CH:11][C:12]=2[CH3:13])=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydride2×HCID 90177836(3-(4-chlorobenzyl)-4-methylphenyl)((3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]-dioxol-5-yl)methanone

Product 1

HCID 90177900(3aS,5S,6R,6aS)-5-((S)-(3-(4-chlorobenzyl)-4-methylphenyl)(hydroxy)-methyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-olYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(3-(4-chlorobenzyl)-4-methyl phenyl)((3aS,5R,6S,6aS)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methanone (4, 26.1 g, 64.9 mmol) and CeCl3.7 H2O (29.0 g, 77.9 mmol) were suspended in 520 mL of MeOH. Sodium borohydride (982 mg, 26.0 mmol, dissolved in 10 mL of 1N aqueous NaOH) was added and the reactants slowly went into solution over about 5 minutes. Another 100 mg (2.6 mmol) of sodium borohydride was added to push the reaction to completion. The reaction was stirred for 10 minutes and quenched with 500 mL of saturated aqueous NH4Cl. Most of the MeOH was removed in vacuo and the residual solvents were diluted with a 1:1 (v:v) solution of saturated aqueous NH4Cl:brine. The aqueous layer was extracted three times with 500 mL of EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated under vacuum. The crude product was used without further purification in the next step (26.2 g, 99% yield, >10:1 d.r.). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.14-7.31 (m, 5 H), 7.04 (d, J=8.3 Hz, 2 H), 6.04 (d, J=3.8 Hz, 1 H), 5.24 (t, J=3.4 Hz, 1H), 4.51 (d, J=3.8 Hz, 1 H), 4.14-4.21 (m, 2 H), 4.04 (d, J=1.5 Hz, 1 H), 3.97 (s, 2 H), 2.77 (d, J=3.0 Hz, 1 H), 2.20-2.27 (m, 3 H), 1.46 (s, 3 H), 1.33 (s, 3 H). MS (ES+) [M+NH4]+=422.

Workup

  1. customthe reaction to completion
  2. customquenched with 500 mL of saturated aqueous NH4Cl
  3. customMost of the MeOH was removed in vacuo
  4. additionthe residual solvents were diluted with a 1:1 (v:v) solution of saturated aqueous NH4Cl
  5. extractionThe aqueous layer was extracted three times with 500 mL of EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe crude product was used without further purification in the next step (26.2 g, 99% yield, >10:1 d.r.)

Sources & evidence

ORD record
ord-e55576bfe2a04bf9b05e10addb27f85f
Source dataset
uspto-grants-2015_12
Patent number
US09200025B2

Reaction notes

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