4-Methylmorpholine → Phenylmethyl (3S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-4-hydroxybutanoate

HRID 1260403Notes

Reaction equation

HRID 1260403 reaction equation
[CH2:1]([O:8][C:9](=[O:23])[CH2:10][C@H:11]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:12](O)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>O1CCCC1.O>[CH2:1]([O:8][C:9](=[O:23])[CH2:10][C@H:11]([NH:15][C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:12][OH:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 1581888N-tert-Butoxycarbonyl-L-aspartic acid beta-benzyl esterHCID 4311764Sodium borohydride

Product 1

HCID 10040985Phenylmethyl (3S)-3-[[(1,1-dimethylethoxy)carbonyl]amino]-4-hydroxybutanoateYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

(S)-2-t-butoxycarbonylamino-succinic acid 4-benzyl ester (545 mg, 1.69 mmol) was dissolved in tetrahydrofuran (THF) to which N-methylmorpholine (NMM, 0.19 mL, 1.77 mmol) and isobutyl chloroformate (0.23 mL, 1.77 mmol) were added at 0° C., followed by stirring at that temperature for 30 min. After 30 min, the resulting white solid salt was removed by celite filtration, and a solution of sodium borohydride (96 mg, 2.53 mmol) in distilled water (2 mL) was added to the resulting clear filtrate without further concentration at room temperature. After stirring for 1 hour at room temperature, THF was distilled under reduced pressure. The reaction was diluted with ethyl acetate and was terminated by the addition of 1N HCl. The organic layer was extracted with ethyl acetate and was purified by column chromatography (ethyl acetate:hexane=1:1) to afford 468 mg (yield: 90%) of the title compound.

Workup

  1. additionwere added at 0° C.
  2. waitAfter 30 min
  3. customthe resulting white solid salt was removed by celite filtration
  4. stirringAfter stirring for 1 hour at room temperature
  5. distillationTHF was distilled under reduced pressure
  6. additionThe reaction was diluted with ethyl acetate
  7. customwas terminated by the addition of 1N HCl
  8. extractionThe organic layer was extracted with ethyl acetate
  9. customwas purified by column chromatography (ethyl acetate:hexane=1:1)

Sources & evidence

ORD record
ord-8ffeddc009f649ed87adccb173767b48
Source dataset
uspto-grants-2013_06
Patent number
US08470836B2

Reaction notes

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