Oxalyl chloride → Oxalyl chloride

HRID 423579Notes

Reaction equation

HRID 423579 reaction equation
[C:1]([Cl:6])(=[O:5])[C:2]([Cl:4])=[O:3].O[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:20]=[CH:19][C:18]([O:21][CH2:22][CH:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][CH:32]([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)=[CH:17][CH:16]=2)=[CH:11][CH:10]=1>C(Cl)Cl.CN(C=O)C>[C:1]([Cl:6])(=[O:5])[C:2]([Cl:4])=[O:3].[Cl:4][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:20]=[CH:19][C:18]([O:21][CH2:22][CH:23]3[CH2:28][CH2:27][N:26]([C:29]([O:31][CH:32]([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]3)=[CH:17][CH:16]=2)=[CH:11][CH:10]=1

Participants

6

Reactant 2

HCID 65578Oxalyl chlorideHCID 66673129HCID 66673129, compound

Product 2

HCID 65578Oxalyl chlorideHCID 66673580HCID 66673580, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (42 μL, 0.47 mmol) was added to a solution of 1-methylethyl 4-[({6-[4-(hydroxymethyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate (0.165 g, 0.43 mmol) in CH2Cl2 (5 mL) and DMF (0.5 mL) at 0° C. The mixture was warmed to ambient temperature and stirred for 1 h. Removal of CH2Cl2 and excess of oxalyl chloride under reduced pressure gave crude 1-methylethyl 4-[({6-[4-(chloromethyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate as a dark brown oil. Crude 1-methylethyl 4-[({6-[4-(chloromethyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate was mixed with sodium thiomethoxide (64 mg, 0.86 mmol) in DMF and heated at 100° C. overnight. Additional sodium thiomethoxide (64 mg, 0.86 mmol) was added, and the heating was continued at 100° C. overnight. Cooled to ambient temperature, the mixture was poured into water and extracted with Et2O. The combined organic extract was washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give a yellow solid. The crude material was purified by chromatography on a silica gel column eluted with 1:11 EtOAc/CH2Cl2 to 1:8 EtOAc/CH2Cl2 to give 32 mg (18%) of 1-methylethyl 4-{[(6-{4-[(methylthio)methyl]phenyl}-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylateas a white solid. LRMS (ESI), m/z 415 (M+H).

Workup

  1. customRemoval of CH2Cl2

Sources & evidence

ORD record
ord-f539e676fb96413eb1a439346d2b6ad3
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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