2,6-Dichlorobenzoyl chloride → (S)-2-tert-butoxycarbonylamino-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid methyl ester

HRID 63716

Reaction equation

HRID 63716 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C@@H:4]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1.[Cl:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[C:24]=1[C:25](Cl)=[O:26].CCN(C(C)C)C(C)C>ClCCl>[CH3:1][O:2][C:3](=[O:21])[C@@H:4]([NH:13][C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:25](=[O:26])[C:24]2[C:23]([Cl:22])=[CH:31][CH:30]=[CH:29][C:28]=2[Cl:32])=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 783922,6-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 110118554-Amino-N-((1,1-dimethylethoxy)carbonyl)-L-phenylalanine methyl ester

Product 1

HCID 54393861(S)-2-tert-butoxycarbonylamino-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid methyl esterYield 88.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-3-[4-aminophenyl]-2-tert-butoxycarbonylamino-propionic acid methyl ester (37.57 g, 127.6 mmol) and 2,6-dichlorobenzoyl chloride (29.45 g, 140.6 mmol) in dichloromethane (350 mL) was added DIPEA (24.8 g, 192 mmol) at room temperature. The brown solution was stirred for 15 h at room temperature to afford a white suspension at this time TLC analysis of the mixture indicated the absence of starting material. Then, the solids were collected by filtration and the solids were washed with dichloromethane (150 mL) and air dried to obtain 52.75 g (88.4% yield) of (S)-2-tert-butoxycarbonylamino-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid methyl ester as a white solid: mp 192-194° C. ES(+)-HRMS m/e calcd. for C22H24Cl2N2O5 (M+H)+ 466.1062, obsd. 466.1069.

Workup

  1. customto afford a white suspension at this time TLC analysis of the mixture
  2. filtrationThen, the solids were collected by filtration
  3. washthe solids were washed with dichloromethane (150 mL) and air
  4. customdried

Sources & evidence

ORD record
ord-ec259c0dcfa745ae80aa81e4c827b872
Source dataset
uspto-grants-2016_09
Patent number
US09447035B2

Linked notes

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