Triethylamine → HCID 66681229, compound

HRID 1626732Notes

Reaction equation

HRID 1626732 reaction equation
C(N(CC)CC)C.CC(C)(C)C(Cl)=O.[C:15]([O:19][C:20]([N:22]1[CH2:29][CH2:28][CH2:27][C@H:23]1[C:24]([OH:26])=O)=[O:21])([CH3:18])([CH3:17])[CH3:16].[NH2:30][C:31]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:32]=1[C:33]([O:35][CH3:36])=[O:34]>O.C1COCC1>[Cl:41][C:38]1[CH:39]=[CH:40][C:31]([NH:30][C:24]([C@@H:23]2[CH2:27][CH2:28][CH2:29][N:22]2[C:20]([O:19][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:21])=[O:26])=[C:32]([C:33]([O:35][CH3:36])=[O:34])[CH:37]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 78878Methyl 2-amino-5-chlorobenzoateHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-

Product 1

HCID 66681229HCID 66681229, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under ice-cooling, 1.73 mL (12.4 mmol) of triethylamine and 0.88 mL (7.23 mmol) of 2,2-dimethyl propanoyl chloride were added to a THF (10 mL) solution comprising 1.50 g (6.97 mmol) of 1-(tert-butoxycarbonyl)-L-proline, and the mixture was stirred under ice-cooling for 30 minutes. Subsequently, 269 mg (4.65 mmol) of methyl 2-amino-5-chlorobenzoate was added thereto under ice-cooling, and the mixture was heated under reflux for 19 hours. After condensation and addition of water, the mixture was extracted with ethyl acetate. The organic layer was washed with 0.1% hydrochloric acid, water, saturated sodium bicarbonate water, and saturated saline, followed by drying over magnesium sulfate. After condensation, the resultant was purified by silica gel column chromatography (n-hexane/ethyl acetate=10/1→4/1), thereby giving 1.65 g of tert-butyl (2S)-2-{[4-chloro-2-(methoxycarbonyl)phenyl]carbamoyl}pyrrolidine-1-carboxylate (yield: 93%).

Workup

  1. temperatureUnder ice-cooling
  2. temperaturecooling for 30 minutes
  3. temperatureunder ice-cooling
  4. temperaturethe mixture was heated
  5. temperatureunder reflux for 19 hours
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with 0.1% hydrochloric acid, water, saturated sodium bicarbonate water, and saturated saline
  8. dry with materialby drying over magnesium sulfate
  9. customAfter condensation
  10. customthe resultant was purified by silica gel column chromatography (n-hexane/ethyl acetate=10/1→4/1)

Sources & evidence

ORD record
ord-371e10f722914970b01fed43b4f2e11c
Source dataset
uspto-grants-2014_07
Patent number
US08785473B2

Reaction notes

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