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

HRID 1053666Notes

Reaction equation

HRID 1053666 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:18][C:19]1[CH:24]=[C:23]([CH2:25][OH:26])[CH:22]=[CH:21][C:20]=1[N+:27]([O-:29])=[O:28])[CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:30][CH2:31][CH2:32][N:33]([CH2:37][CH2:38][Cl:39])[C:34](Cl)=[O:35]>N1C=CC=CC=1>[Cl:30][CH2:31][CH2:32][N:33]([CH2:37][CH2:38][Cl:39])[C:34]([O:26][CH2:25][C:23]1[CH:22]=[CH:21][C:20]([N+:27]([O-:29])=[O:28])=[C:19]([CH2:18][C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:10][C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12])[CH:24]=1)=[O:35]

Participants

4

Reactant 2

HCID 76346Bis(2-chloroethyl)carbamoyl chlorideHCID 118276599tert-Butyl (3R)-3-(tert-butoxycarbonylamino)-4-[5-(hydroxymethyl)-2-nitro-phenyl]butanoate

Product 1

HCID 118276712tert-Butyl (3R)-4-[5-[bis(2-chloroethyl)carbamoyloxymethyl]-2-nitro-phenyl]-3-(tert-butoxycarbonylamino)butanoate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Adapting a literature known protocol (Fex, et al., U.S. Pat. No. 3,299,104), tert-butyl(3R)-4-[5-[bis(2-chloroethyl)carbamoyloxymethyl]-2-nitro-phenyl]-3-(tert-butoxycarbonylamino)butanoate (20b) is prepared through carbamoylation of tert-butyl(3R)-3-(tert-butoxycarbonylamino)-4-[5-(hydroxymethyl)-2-nitro-phenyl]butanoate (20a) (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 (20b).

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-e1dcabfae4224641a135e5af11f6fa6e
Source dataset
uspto-grants-2016_07
Patent number
US09394237B2

Reaction notes

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