Phosgene → HCID 11477361, compound

HRID 1866859Notes

Reaction equation

HRID 1866859 reaction equation
[C:1](Cl)(Cl)=[O:2].[C:5]1([C:11]2([C:18]3[CH:27]=[C:26]([O:28][CH2:29][C:30]4[CH:39]=[CH:38][C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[N:31]=4)[CH:25]=[CH:24][C:19]=3[C:20]([NH:22][NH2:23])=[O:21])[CH2:16][CH:15]3[CH2:17][CH:12]2[CH2:13][CH2:14]3)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl>[C:5]1([C:11]2([C:18]3[CH:27]=[C:26]([O:28][CH2:29][C:30]4[CH:39]=[CH:38][C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[N:31]=4)[CH:25]=[CH:24][C:19]=3[C:20]3[O:21][C:1](=[O:2])[NH:23][N:22]=3)[CH2:16][CH:15]3[CH2:17][CH:12]2[CH2:13][CH2:14]3)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 57978651HCID 57978651, compound

Product 1

HCID 11477361HCID 11477361, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

Phosgene (751 μL of a −20% w/v solution in toluene, 1.42 mmol) was added dropwise via syringe to a stirred solution of 4d (365 mg, 0.79 mmol) in methylene chloride (20 mL) at −78° C. After approximately 45 minutes, the reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted three times with methylene chloride. The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo. The crude residue was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (gradient elution; 0-75% acetonitrile/water as eluent, 0.1% TFA as modifier). Lyophilization of the purified fractions afforded the title compound 4e, m/z (ES) 490 (MH)+.

Workup

  1. extractionextracted three times with methylene chloride
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was purified by preparative reversed phase HPLC on YMC Pack Pro C18 stationary phase (gradient elution; 0-75% acetonitrile/water as eluent, 0.1% TFA as modifier)

Sources & evidence

ORD record
ord-8dd638fe237c4bd1a16ba776b19babc1
Source dataset
uspto-grants-2009_12
Patent number
US07629467B2

Reaction notes

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