Ammonia → HCID 67115807, compound

HRID 1844247Notes

Reaction equation

HRID 1844247 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:28][C:29]([OH:31])=O)[C@@H:9]1[CH2:11][C@H:10]1[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=2)=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH3:32]>C(Cl)Cl>[NH2:32][C:29](=[O:31])[CH2:28][N:8]([C@@H:9]1[CH2:11][C@H:10]1[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=2)=[CH:14][CH:13]=1)[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 222AmmoniaHCID 70872795HCID 70872795, compound

Product 1

HCID 67115807HCID 67115807, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N,N′-Carbonyldiimidazole (27 mg, 0.17 mmol) was added to a solution of [(tert-butoxycarbonyl){(trans)-2-{4-[(4-cyanobenzyl)oxy]phenyl}cyclopropyl}amino]acetic acid (50 mg, 0.12 mmol) in dry CH2Cl2 (3 mL) at 0° C. (ice-water bath). The solution was stirred for 40 min at room temperature and cooled again at 0° C.; NH3 (25% aqueous solution, 0.05 mL, 0.60 mmol) was added and the reaction was allowed to reach room temperature and stirred for additional 1.5 h. The mixture was diluted with CH2Cl2 (20 mL) and washed with brine (10 mL) and HCl (10% aqueous solution, 1 mL). The organic layer was dried over anhydrous Na2SO4 and filtered. After removal of the solvent, the crude product was purified by column chromatography on silica gel (5% MeOH/CH2Cl2) affording 38 mg of tert-butyl 2-amino-2-oxoethyl[(trans)-2-{4-[(4-cyanobenzyl)oxy]phenyl}cyclopropyl]carbamate [Rf=0.6 (10% MeOH/CH2Cl2), colorless oil, 76% yield].

Workup

  1. temperaturecooled again at 0° C.
  2. customto reach room temperature
  3. stirringstirred for additional 1.5 h
  4. washwashed with brine (10 mL) and HCl (10% aqueous solution, 1 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customAfter removal of the solvent
  8. customthe crude product was purified by column chromatography on silica gel (5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-a76b7195360d412ebbe7bb2558210007
Source dataset
uspto-grants-2015_02
Patent number
US08946296B2

Reaction notes

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