Ammonia → (R)-1-benzyl ethyl 3-t-butyloxycarbonylamino-3-carbamoylsuccinate

HRID 57753Notes

Reaction equation

HRID 57753 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]([C:24]([O:26][CH2:27][CH3:28])=[O:25])([C:21](O)=[O:22])[CH2:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OCC(C)C)=O.[NH3:37].Cl>C1COCC1.C(N(CC)CC)C>[C:1]([O:5][C:6]([NH:8][C@:9]([C:21](=[O:22])[NH2:37])([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 62365Isobutyl chloroformateHCID 66725181(R)-1-benzyl hydrogen 3-t-butyloxycarbonylamino-3-ethoxycarbonylsuccinate

Product 1

HCID 66725258(R)-1-benzyl ethyl 3-t-butyloxycarbonylamino-3-carbamoylsuccinateYield 55%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

A solution of (R)-1-benzyl hydrogen 3-t-butyloxycarbonylamino-3-ethoxycarbonylsuccinate (1.0 g) obtained in Example 19 in THF (20 mL) was added with triethylamine (0.62 mL) and isobutyl chloroformate (0.55 mL, 0.57 g) in this order at −15° C. with stirring, and the mixture was stirred for 30 minutes. A solution of 25% aqueous ammonia (0.30 mL) was dropped into the reaction mixture at the same temperature. The reaction mixture was stirred at the same temperature for 30 minutes, and then poured into diluted hydrochloric acid, the mixture was extracted with ethyl acetate, and then the extract was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was subjected to silica gel column chromatography, in which elution was performed with n-hexane/ethyl acetate (1:1) for purification, and then crystallized from ethyl acetate/n-hexane to obtain the title compound (0.60 g, yield: 55%) as colorless crystals. Optical rotation [α]D25 was +1.28° (c 0.50, ethanol).

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. stirringThe reaction mixture was stirred at the same temperature for 30 minutes
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialthe extract was dried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. washthe residue was subjected to silica gel column chromatography, in which elution
  7. customwas performed with n-hexane/ethyl acetate (1:1) for purification
  8. customcrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-c37161d2f3644f459e85e79a4a101e15
Source dataset
uspto-grants-2016_09
Patent number
US09434737B2

Reaction notes

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