Bis(2-chloroethyl)carbamoyl chloride → tert-Butyl 3-[5-[bis(2-chloroethyl)carbamoyloxy]-2-methyl-phenyl]-4-(tert-butoxycarbonylamino)butanoate

HRID 1053706Notes

Reaction equation

HRID 1053706 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]([C:19]1[CH:24]=[C:23]([OH:25])[CH:22]=[CH:21][C:20]=1[CH3:26])[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:27][CH2:28][CH2:29][N:30]([CH2:34][CH2:35][Cl:36])[C:31](Cl)=[O:32]>N1C=CC=CC=1>[Cl:27][CH2:28][CH2:29][N:30]([CH2:34][CH2:35][Cl:36])[C:31]([O:25][C:23]1[CH:22]=[CH:21][C:20]([CH3:26])=[C:19]([CH:10]([CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:11][C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH:24]=1)=[O:32]

Participants

4

Reactant 2

HCID 76346Bis(2-chloroethyl)carbamoyl chlorideHCID 118277046tert-Butyl 4-(tert-butoxycarbonylamino)-3-(5-hydroxy-2-methyl-phenyl)butanoate

Product 1

HCID 118276980tert-Butyl 3-[5-[bis(2-chloroethyl)carbamoyloxy]-2-methyl-phenyl]-4-(tert-butoxycarbonylamino)butanoate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Adapting a literature known protocol (U.S. Pat. No. 3,299,104), tert-butyl 3-[5-[bis(2-chloroethyl)carbamoyloxy]-2-methyl-phenyl]-4-(tert-butoxycarbonylamino)butanoate (23e) is prepared through carbamoylation of tert-butyl 4-(tert-butoxycarbonylamino)-3-(5-hydroxy-2-methyl-phenyl)butanoate (23d) (731 mg, 2.0 mmol) with commercial N,N-bis(2-chloroethyl)carbamoyl chloride (439 μL, 614 mg, 3.0 mmol) in anhydrous pyridine (15 mL) at about 0° C. The reaction mixture is stirred with gradual warming to room temperature. The reaction is monitored by TLC and/or LC/MS to completion. Excess of the carbamoyl chloride is destroyed with crushed ice. Aqueous work-up followed by purification through silica gel column chromatography afford the title compound.

Workup

  1. customExcess of the carbamoyl chloride is destroyed with crushed ice
  2. customAqueous work-up followed by purification through silica gel column chromatography

Sources & evidence

ORD record
ord-a24794b1426c42008815ef84bc34cf67
Source dataset
uspto-grants-2016_07
Patent number
US09394236B2

Reaction notes

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