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

HRID 346950Notes

Reaction equation

HRID 346950 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)carboxylate2×HCID 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=7.3 Hz), 5.03 (sept., 1H, J=6.2 Hz), 4.28 (br d, 1H, J=6.2 Hz), 3.67 (br dd, J=10.2, 5.5 Hz), 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=6.2 Hz), 1.23 (d, 3H, J=6.2 Hz). 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-308a7cd7a68f4a4f80d0327cd5830418
Source dataset
uspto-grants-2007_02
Patent number
US07173004B2

Reaction notes

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