Diphosgene → HCID 86646168, compound

HRID 602291Notes

Reaction equation

HRID 602291 reaction equation
ClC([O:4][C:5](Cl)(Cl)Cl)=O.Cl.[CH3:10][O:11][NH:12][CH3:13].[NH2:14][C:15]1[C:37]([Cl:38])=[CH:36][C:18]([C:19]([NH:21][CH2:22][C@@H:23]2[O:28][CH2:27][CH2:26][N:25]([CH2:29][CH:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[CH2:24]2)=[O:20])=[C:17]([O:39][CH2:40][CH3:41])[CH:16]=1>C(Cl)Cl>[NH2:14][C:15]1[C:37]([Cl:38])=[CH:36][C:18]([C:19]([NH:21][CH2:22][C@@H:23]2[O:28][CH2:27][CH2:26][N:25]([CH2:29][CH:30]3[CH2:31][CH2:32][N:33]([C:5](=[O:4])[N:12]([O:11][CH3:10])[CH3:13])[CH2:34][CH2:35]3)[CH2:24]2)=[O:20])=[C:17]([O:39][CH2:40][CH3:41])[CH:16]=1

Participants

5

Reactant 3

HCID 10426DiphosgeneHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 67055698HCID 67055698, compound

Product 1

HCID 86646168HCID 86646168, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of trichloromethyl chloroformate (0.15 ml) and O,N-dimethylhydroxyamine hydrochloride (0.24 g) in methylene chloride (10 ml) was added TEA (1.02 ml) at room temperature, and the mixture was stirred for 1 hour. The suspension was added dropwise to a solution of (S)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-piperidinylmethyl)-2-morpholinyl]methyl]benzamide (Example 26) (1.0 g) in methylene chloride (10 ml) under ice cooling. After completion of addition, the internal temperature of the reaction solution was warmed to room temperature, and the solution was stirred for 2 hours. The reaction solution was washed with water, then brine, and then dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol=10/1) to give the titled compound (0.8 g) as a white solid. Melting point 127-129° C. (recrystallized from EA/H)

Workup

  1. additionAfter completion of addition
  2. stirringthe solution was stirred for 2 hours
  3. washThe reaction solution was washed with water
  4. dry with materialbrine, and then dried over anhydrous magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customThe residue was purified by silica gel column chromatography (eluent: chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-e9d0e8977efa41d7a45e77990d2c127f
Source dataset
uspto-grants-2011_03
Patent number
US07906510B2

Reaction notes

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