4-Methylmorpholine → (S)-methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate

HRID 451835Notes

Reaction equation

HRID 451835 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC)=O.[BH4-].[Na+].OS([O-])(=O)=O.[K+]>C1COCC1.CO>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:10][OH:11])[CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 516920Potassium bisulfateHCID 4311764Sodium borohydrideHCID 7018756(S)-2-((tert-butoxycarbonyl)amino)-5-methoxy-5-oxopentanoic acid

Product 1

HCID 11107667(S)-methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoateYield 72%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (S)-2-(tert-butoxycarbonylamino)-5-methoxy-5-oxopentanoic acid (35.2 g, 0.135 mol) in THF (500 mL) at −10° C. was added N-methylmorpholine (15 mL, 0.135 mol) followed by ethyl chloroformate (14.72 g, 0.135 mol). After 10 min, NaBH4 (15.37 g, 0.405 mol) was added in one portion. MeOH (1200 mL) was then added dropwise to the mixture over a period of 20 min at 0° C. The solution was stirred for an additional 20 min and then neutralized with 1M KHSO4. The organic solvent was removed and the aqueous layer was extracted with EtOAc (3×500 ml). The combined organic phases were washed consecutively with 1M KHSO4 (300 mL), H2O (300 mL), 5% aqueous NaHCO3 (300 mL), and dried (Na2SO4). The solvent was evaporated to give a residue, which was purified by column chromatography to give the desired (S)-methyl 4-(tert-butoxycarbonylamino)-5-hydroxypentanoate (24 g, 72%)

Workup

  1. customThe organic solvent was removed
  2. extractionthe aqueous layer was extracted with EtOAc (3×500 ml)
  3. washThe combined organic phases were washed consecutively with 1M KHSO4 (300 mL), H2O (300 mL), 5% aqueous NaHCO3 (300 mL)
  4. dry with materialdried (Na2SO4)
  5. customThe solvent was evaporated
  6. customto give a residue, which
  7. customwas purified by column chromatography

Sources & evidence

ORD record
ord-02345653e2fc4fceb948d62e83c1a568
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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