4-Methylmorpholine → Methyl (S)-3-(Boc-amino)-4-hydroxybutanoate

HRID 2355479Notes

Reaction equation

HRID 2355479 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]([O:16][CH3:17])=[O:15])[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC)=O.[BH4-].[Na+].C([O-])(O)=O.[Na+]>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:10][OH:11])[CH2:13][C:14]([O:16][CH3:17])=[O:15])=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 10977771(2S)-2-{[(tert-butoxy)carbonyl]amino}-4-methoxy-4-oxobutanoic acid

Product 1

HCID 54573797Methyl (S)-3-(Boc-amino)-4-hydroxybutanoateYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-2-(tert-butoxycarbonylamino)-4-methoxy-4-oxobutanoic acid (9.0 g, 35.7 mmol) in THF (180 mL) at −10° C. was added N-methylmorpholine (3.9 mL, 35.7 mmol) followed by ethyl chloroformate (3.91 g, 35.7 mmol). After 10 min, the mixture was transferred slowly to a mixture of NaBH4 (2.7 g, 71.4 mmol) and ice water (900 mL). The resulting solution was stirred for 1 h, NaHCO3 (˜20 g) was added, and the organic layer was separated. The aqueous layer was extracted with EtOAc (4×200 mL). The combined organic layers were washed with 1 N aq HCl (20 mL) and brine (15 mL), dried over Na2SO4, and concentrated to give (S)-methyl 3-(tert-butoxycarbonylamino)-4-hydroxybutanoate (7.06 g, 85%) as an oil. MS m/z 234 (M+H+).

Workup

  1. customthe organic layer was separated
  2. extractionThe aqueous layer was extracted with EtOAc (4×200 mL)
  3. washThe combined organic layers were washed with 1 N aq HCl (20 mL) and brine (15 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-784059009fbf4d0fb00d4383a8bebea9
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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