1-Hydroxybenzotriazole → {(R)-[4-(2-tert-butoxy-ethoxy)-phenyl]-[(S)-1-(2-fluoro-4-iodo-phenylcarbamoyl)-3,3-dimethyl-butylcarbamoyl]-methyl}-carbamic acid tert-butyl ester

HRID 1433775Notes

Reaction equation

HRID 1433775 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:18])[CH:11]([NH2:17])[CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14].[C:19]([O:23][C:24]([NH:26][C@H:27]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[CH:33][CH:32]=1)[C:28](O)=[O:29])=[O:25])([CH3:22])([CH3:21])[CH3:20].ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[C:19]([O:23][C:24](=[O:25])[NH:26][C@H:27]([C:31]1[CH:32]=[CH:33][C:34]([O:37][CH2:38][CH2:39][O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[CH:35][CH:36]=1)[C:28](=[O:29])[NH:17][C@H:11]([C:10](=[O:18])[NH:9][C:3]1[CH:4]=[CH:5][C:6]([I:8])=[CH:7][C:2]=1[F:1])[CH2:12][C:13]([CH3:14])([CH3:15])[CH3:16])([CH3:21])([CH3:22])[CH3:20]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66815165(R)-tert-butoxycarbonylamino-[4-(2-tert-butoxy-ethoxy)-phenyl]-acetic acidHCID 693041852-Amino-4,4-dimethyl-pentanoic acid(2-fluoro-4-iodo-phenyl)-amide

Product 1

HCID 68619010{(R)-[4-(2-tert-butoxy-ethoxy)-phenyl]-[(S)-1-(2-fluoro-4-iodo-phenylcarbamoyl)-3,3-dimethyl-butylcarbamoyl]-methyl}-carbamic acid tert-butyl esterYield 91.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of 2-amino-4,4-dimethyl-pentanoic acid (2-fluoro-4-iodo-phenyl)-amide (364 mg, 1 mmol), (R)-tert-butoxycarbonylamino-[4-(2-tert-butoxy-ethoxy)-phenyl]-acetic acid (1 M in DMF, 1.1 mL, 1.1 mmol), 1-Hydroxybenzotriazole (168 mg, 1.1 mmol) and diisopropylethyl amine (0.53 mL, 3.3 mmol) in N,N-dimethylformamide (5 mL) was added dropwise the solution of O-benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)uronium hexaflurorophosphate (474 mg, 1.1 mmol). The reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate and the mixture washed with water and brine. The organic layers were successively washed with 1 M aqueous citric acid solution, brine, saturated aqueous sodium carbonate, brine, dried over sodium sulfate, filtered, and concentrated to give {(R)-[4-(2-tert-butoxy-ethoxy)-phenyl]-[(S)-1-(2-fluoro-4-iodo-phenylcarbamoyl)-3,3-dimethyl-butylcarbamoyl]-methyl}carbamic acid tert-butyl ester (652 mg, 91%) as a white solid.

Workup

  1. washthe mixture washed with water and brine
  2. washThe organic layers were successively washed with 1 M aqueous citric acid solution, brine, saturated aqueous sodium carbonate, brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d907383d83a249b3b54092c9f7e18844
Source dataset
uspto-grants-2009_11
Patent number
US07612212B2

Reaction notes

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