Triethylamine → Methyl 3-((tert-butoxycarbonyl)amino)-4-hydroxybutanoate

HRID 1435954Notes

Reaction equation

HRID 1435954 reaction equation
[CH3:1][O:2][C:3](=[O:17])[CH2:4][CH:5]([NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:6](O)=[O:7].CCN(CC)CC.ClC(OCC)=O.[BH4-].[Na+].OS([O-])(=O)=O.[Na+]>C1COCC1.CO>[CH3:1][O:2][C:3](=[O:17])[CH2:4][CH:5]([NH:9][C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH2:6][OH:7]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 516919Sodium BisulfateHCID 41047422-((tert-Butoxycarbonyl)amino)-4-methoxy-4-oxobutanoic acidHCID 4311764Sodium borohydride

Product 1

HCID 23590716Methyl 3-((tert-butoxycarbonyl)amino)-4-hydroxybutanoateYield 35%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of DL-2-tert-butoxycarbonylamino-succinic acid 4-methyl ester (5 g, 0.02 mol) in dry THF (100 mL) at −10° C. Et3N (3.1 mL, 0.022 mol) was added, followed by ethyl chloroformate (2.1 mL, 0.022 mol). After 10 min, NaBH4 (2.27 g, 0.06 mol) was added and then MeOH was dropped into the mixture over a period of 20 min at 0° C. The reaction mixture was stirred for 1 hour at 0° C. and for 2 hours at room temperature then neutralized with sat. aq. NaHSO4. The organic solvent was removed and the product was extracted with AcOEt three times. The combined organic phases were washed consecutively with sat. aq. NaHSO4, water, sat. aq. NaHCO3, water and dried over anh. Na2SO4. The solvent was evaporated and the residue was purified by flash chromatography (n-hexane/AcOEt 5:1), affording the title compound (1.63 g, 35%).

Workup

  1. customat −10° C
  2. customThe organic solvent was removed
  3. extractionthe product was extracted with AcOEt three times
  4. washThe combined organic phases were washed consecutively with sat. aq. NaHSO4, water, sat. aq. NaHCO3, water
  5. dry with materialdried over anh. Na2SO4
  6. customThe solvent was evaporated
  7. customthe residue was purified by flash chromatography (n-hexane/AcOEt 5:1)

Sources & evidence

ORD record
ord-766469768c5d4a5cb971ca9fd9814c5f
Source dataset
uspto-grants-2009_11
Patent number
US07618982B2

Reaction notes

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