Methanol → HCID 59201656, compound

HRID 451876Notes

Reaction equation

HRID 451876 reaction equation
[CH:1]1([O:7][C:8](=[O:41])[CH2:9][CH2:10][C@@H:11]([C:27](N2[C@H](C3C=CC=CC=3)COC2=O)=[O:28])[CH2:12][C@H:13]2[CH2:17][O:16][C:15]([CH3:19])([CH3:18])[N:14]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CO.[BH4-].[Na+]>C1COCC1>[CH:1]1([O:7][C:8](=[O:41])[CH2:9][CH2:10][C@@H:11]([CH2:27][OH:28])[CH2:12][C@H:13]2[CH2:17][O:16][C:15]([CH3:18])([CH3:19])[N:14]2[C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydride2×HCID 59201379HCID 59201379, compound

Product 1

HCID 59201656HCID 59201656, compoundYield 90.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The (S)-tert-butyl 4-((R)-5-(cyclohexyloxy)-5-oxo-2-((R)-2-oxo-4-phenyloxazolidine-3-carbonyl)pentyl)-2,2-dimethyloxazolidine-3-carboxylate (8.12 g, 13.9 mmol, 1.0 equiv) was dissolved in a 4:1 mixture of THF:MeOH (150 mL) and the solution cooled to 0° C. Solid NaBH4 (1.05 g, 27.8 mmol, 2.0 equiv) was added in ca 200 mg portions over a 20 min period. The solution was stirred at 0° C. for 4 h. During this time two additional 500 mg portions of NaBH4 were added. After this time LC/MS analysis showed consumption of the starting material. The excess hydride reagent was quenched by the addition of 10,% citric acid. The mixture was diluted with ca 100 mL of EtOAc and the organic layer separated. The aqueous layer was extracted with additional EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated. The alcohol was purified by flash chromatography on silica, (120 g), eluting with 0-41% EtOAc in hexanes. This afforded 5.2 g (90% yield) of (S)-tert-butyl 4-((R)-5-(cyclohexyloxy)-2-(hydroxymethyl)-5-oxopentyl)-2,2-dimethyloxazolidine-3-carboxylate as a clear syrup. MS ESI +ve m/z 436 (M+Na).

Workup

  1. customconsumption of the starting material
  2. customThe excess hydride reagent was quenched by the addition of 10,% citric acid
  3. additionThe mixture was diluted with ca 100 mL of EtOAc
  4. customthe organic layer separated
  5. extractionThe aqueous layer was extracted with additional EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe alcohol was purified by flash chromatography on silica, (120 g)
  11. washeluting with 0-41% EtOAc in hexanes

Sources & evidence

ORD record
ord-6edbb9f065d749afa334adee2939ef84
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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