Water → HCID 131728697, compound

HRID 554777Notes

Reaction equation

HRID 554777 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C@H:10]([CH2:14][C:15]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=1[O:22][CH3:23])[C:11](O)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)([N:26]1C=CN=C1)=O.O.N.O>O1CCCC1.C(OCC)(=O)C>[NH2:26][C:11](=[O:12])[C@@H:10]([CH2:14][C:15]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=1[O:22][CH3:23])[CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 12896473Azane;hydrateHCID 66935162(2S)-3-[(tert-butoxycarbonyl)amino]-2-(5-chloro-2-methoxybenzyl)propanoic acid

Product 1

HCID 131728697HCID 131728697, compoundYield 97.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(Step 3) To (2S)-3-[(tert-butoxycarbonyl)amino]-2-(5-chloro-2-methoxybenzyl)propanoic acid (30 g) in tetrahydrofuran (150 ml) solution, 1,1′-carbonyldiimidazole (15.6 g) was added under ice cooling and the mixture was stirred at room temperature for 1 hour. The reaction solution was cooled to 0° C., 28% ammonia water (30 ml) was added, and the mixture was stirred at room temperature for 30 minutes. Distilled water and ethyl acetate were added to the reaction solution, the aqueous layer and the organic layer were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was successively washed with saturated potassium hydrogensulfate aqueous solution and saturated saline, dried over with anhydrous sodium sulfate, then concentrated. Hexane and ethyl acetate were added to the precipitated solid and the mixture was stirred in the suspended state at room temperature. The precipitated solid was collected by filtration to obtain the title compound (29.2 g).

Workup

  1. temperatureThe reaction solution was cooled to 0° C.
  2. stirringthe mixture was stirred at room temperature for 30 minutes
  3. customthe aqueous layer and the organic layer were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layer was successively washed with saturated potassium hydrogensulfate aqueous solution and saturated saline
  6. dry with materialdried over with anhydrous sodium sulfate
  7. concentrationconcentrated
  8. additionHexane and ethyl acetate were added to the precipitated solid
  9. stirringthe mixture was stirred in the suspended state at room temperature
  10. filtrationThe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-f93a40ee12074be98e5bc52b4aad0a6c
Source dataset
uspto-grants-2011_11
Patent number
US08049006B2

Reaction notes

Loading…