Chloromethyl chloroformate → Chloromethyl [4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)benzyl]carbamate

HRID 1013533Notes

Reaction equation

HRID 1013533 reaction equation
[NH2:1][CH2:2][C:3]1[CH:30]=[CH:29][C:6]([C:7]([NH:9][C:10]2[CH:15]=[C:14]([C:16]3[S:17][CH:18]=[CH:19][CH:20]=3)[CH:13]=[CH:12][C:11]=2[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:8])=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.[Cl:40][CH2:41][O:42][C:43](Cl)=[O:44]>ClCCl>[C:24]([O:23][C:22]([NH:21][C:11]1[CH:12]=[CH:13][C:14]([C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)=[CH:15][C:10]=1[NH:9][C:7]([C:6]1[CH:29]=[CH:30][C:3]([CH2:2][NH:1][C:43](=[O:44])[O:42][CH2:41][Cl:40])=[CH:4][CH:5]=1)=[O:8])=[O:28])([CH3:25])([CH3:26])[CH3:27]

Participants

5

Reactant 3

HCID 62754Chloromethyl chloroformateHCID 81531DiisopropylethylamineHCID 57925930Tert-butyl [2-{[4-(aminomethyl)benzoyl]amino}-4-(2-thienyl)phenyl]carbamate

Product 1

HCID 57925931Chloromethyl [4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)benzyl]carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

tert-butyl [2-{[4-(aminomethyl)benzoyl]amino}-4-(2-thienyl)phenyl]carbamate (2.0 g, 4.72 mmol) was suspended in dichloromethane (50 ml). Hunig's Base (1 ml, 5.73 mmol) was added. The solution was cooled to 0° C. Chlorocarbonic acid chloromethyl ester (0.5 ml, 5.68 mmol) was added slowly. The reaction was stirred for approximately 1-2 h. The mixture, while cold, was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate. The aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried over Na2SO4, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with EtOAc/hexane. MS: calc'd 417 (MH+-Boc), exp 417 (MH+-Boc).

Workup

  1. washwashed with saturated aqueous sodium bicarbonate
  2. extractionThe aqueous layer was extracted three times with dichloromethane
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel eluting with EtOAc/hexane

Sources & evidence

ORD record
ord-d95396bec2604080a6237d1976627d96
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

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