Sodium borohydride → tert-butyl[(2S)-1-{[tert-butyl(diphenyl)silyl]oxy}-6-hydroxyhexan-2-yl]carbamate

HRID 1524345Notes

Reaction equation

HRID 1524345 reaction equation
C(OC(=O)N[C:8](=[O:40])[CH2:9][CH2:10][CH2:11][C@H:12]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:13][O:14][Si:15]([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(C)(C)C.[BH4-].[Na+]>CC(O)C.O>[C:36]([O:35][C:33](=[O:34])[NH:32][C@@H:12]([CH2:11][CH2:10][CH2:9][CH2:8][OH:40])[CH2:13][O:14][Si:15]([C:28]([CH3:29])([CH3:30])[CH3:31])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)([CH3:39])([CH3:37])[CH3:38]

Participants

5

Reactant 2

HCID 4311764Sodium borohydride2×HCID 89938443tert-butyl[(5S)-5-[(tert-butoxycarbonyl)amino]-6-{[tert-butyl(diphenyl)silyl]oxy}hexanoyl]carbamate

Product 1

HCID 89938349tert-butyl[(2S)-1-{[tert-butyl(diphenyl)silyl]oxy}-6-hydroxyhexan-2-yl]carbamateYield 62.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

To a stirred solution of the material from Step 3 (128 g, 219 mmol) in 2-propanol (1800 mL) and water (180 mL) at room temperature was added sodium borohydride (8.28 g, 219 mmol). The reaction mixture was stirred at room temperature overnight. Additional 2 g of sodium borohydride was added and stirred at room temperature for an additional 4 hours. The reaction mixture was concentrated to ⅓ volume and diluted with EtOAc and 1 N NaOH (100 mL). The reaction mixture was partitioned, and extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel using EtOAc-hexanes (0 to 50%) to afford 65 g of the title compound. 1H NMR (CHCl3-d): δ 7.67-7.62 (m, 4H), 7.45-7.35 (m, 6H), 4.72-4.65 (b, 1H), 3.72-3.62 (m, 2H), 3.60-3.52 (m, 3H), 1.62-1.42 (m, 4H), 1.42 (s, 9H), 1.42-1.23 (m, 2H), 1.05 (s, 9H).

Workup

  1. stirringstirred at room temperature for an additional 4 hours
  2. concentrationThe reaction mixture was concentrated
  3. additiondiluted with EtOAc and 1 N NaOH (100 mL)
  4. customThe reaction mixture was partitioned
  5. extractionextracted with EtOAc
  6. washThe combined organics were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-1fc34a7d23f0442fbb866fd0d1bc94d9
Source dataset
uspto-grants-2015_07
Patent number
US09079834B2

Reaction notes

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