Sodium borohydride → isopropyl 2(S)-(tert-butoxycarbonylamino)-5-hydroxypentanoate

HRID 500375Notes

Reaction equation

HRID 500375 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12](=[O:13])[CH2:11][CH2:10][C@H:9]1[C:14]([O:16][CH:17]([CH3:19])[CH3:18])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].C(OCC)(=O)C.CCCCCC>CO.O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:10][CH2:11][CH2:12][OH:13])[C:14]([O:16][CH:17]([CH3:19])[CH3:18])=[O:15])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 4311764Sodium borohydrideHCID 21080141Isopropyl 1-(tert-butoxycarbonyl)pyrrolidin-5-one-2(s)carboxylateHCID 21226206Ethyl acetate hexane

Product 1

HCID 21080142isopropyl 2(S)-(tert-butoxycarbonylamino)-5-hydroxypentanoateYield 64%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of isopropyl 1-(tert-butoxycarbonyl)pyrrolidin-5-one-2(S)-carboxylate (product of step 26B, 49.5 g, 183 mmol) in methanol (300 mL) was added sodium borohydride (10.0 g, 263 mmol) in ˜1 g portions over 1.5 hours. The reaction was stirred under nitrogen for another 10 minutes. It was diluted with water, extracted with ether, combined organic fractions washed with saturated aqueous NaCl, dried (MgSO4) and evaporated to give a light yellow oil. Flash chromatography (silica gel, 20-30% ethyl acetate/hexane) gave 31.8 g (64%) of isopropyl 2(S)-(tert-butoxycarbonylamino)-5-hydroxypentanoate as a colorless syrup: 1H NMR (300 MHz, Chloroform-D) δ 5.16 (br d, 1H, J=7.3Hz), 5.03 (sept., 1H, J=6.2Hz), 4.28 (br d, 1H, J=6.2Hz), 3.67 (br dd, J=10.2, 5.5Hz), 1.94-1.79 (m, 2H), 1.76-1.67 (m, 1H), 1.66-1.56 (m, 2H), 1.43 (s, 9H), 1.25 (d, 3H, J=6.2Hz), 1.23 (d, 3H, J=6.2Hz). LCMS m/z 276 (M+H)+.

Workup

  1. extractionextracted with ether
  2. washwashed with saturated aqueous NaCl
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customto give a light yellow oil

Sources & evidence

ORD record
ord-a7696503ad224d25950b7b9c1021e865
Source dataset
uspto-grants-2010_08
Patent number
US07772183B2

Reaction notes

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