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

HRID 393487Notes

Reaction equation

HRID 393487 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=1)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[Cl:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[C:24]=1[C:25](Cl)=[O:26].C(N(C(C)C)CC)(C)C>ClCCl>[CH3:1][O:2][C:3](=[O:21])[C@H:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:25]([C:24]2[C:23]([Cl:22])=[CH:31][CH:30]=[CH:29][C:28]=2[Cl:32])=[O:26])=[CH:16][CH:15]=1)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:10])[CH3:11])=[O:7]

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 4-amino-N-[(1,1-dimethylethoxy)carbonyl]-L-phenylalanine methyl ester (127.6 mmol, 37.57 g) and 2,6-dichlorobenzoyl chloride (140.6 mmol, 29.45 g) in dichloromethane (350 mL) was added diisopropylethylamine (192 mmol, 33.4 mL) 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. The solids were collected by filtration and were washed with dichloromethane (150 mL) and air dried to obtain 52.75 g (88.4%) of a white solid: mp 192-194° C. 1H NMR (DMSO-d6) (400 MHz) δ 10.68 (s, 1H), 7.47-7.6 (m, 5H), 7.2-7.29 (m, 3H), 4.12-4.17 (m, 1H), 3.62 (s, 3H), 2.79-2.99 (m, 2H), 1.33 (s, 9H), 13C NMR, CDCl3 (100 Mhz) d 172.49, 161.82, 155.37, 136.99, 136.36, 131.28, 131.16, 129.48, 128.19, 119.31, 78.27, 55.3, 51.76, 35.9, 27.77. HR MS: Obs. mass, 466.1069. Calcd. mass, 466.1062).

Workup

  1. customto afford a white suspension
  2. filtrationThe solids were collected by filtration
  3. washwere washed with dichloromethane (150 mL) and air
  4. customdried

Sources & evidence

ORD record
ord-6a89818e15564c578207db035bdb7cab
Source dataset
uspto-grants-2004_10
Patent number
US06806365B2

Reaction notes

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