Chloroacetyl chloride → 2-Chloro-1-[6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-ethanone hydrochloride

HRID 1475520Notes

Reaction equation

[F:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][C:7]2[CH:8]=[C:9]3[NH:15][CH2:14][C:13]([CH3:17])([CH3:16])[C:10]3=[N:11][CH:12]=2)=[CH:4][CH:3]=1.[Cl:20][CH2:21][C:22](Cl)=[O:23]>C(#N)C>[ClH:20].[Cl:20][CH2:21][C:22]([N:15]1[C:9]2[C:10](=[N:11][CH:12]=[C:7]([CH2:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:19][CH:18]=3)[CH:8]=2)[C:13]([CH3:17])([CH3:16])[CH2:14]1)=[O:23]

Participants

Conditions

Temperature: 20 °C

Procedure

To a stirred suspension of 6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine (6.68 g, 26 mol) in acetonitrile (20 mL) at 20° C. was added, steadily over 0.2 h, a solution of chloroacetyl chloride (3.83 g, 2.7 mL, 33.9 mmol) in acetonitrile (10 mL), maintaining the reaction mixture at or below 20° C. using an external ice-methanol bath. A clear solution resulted then, as the internal temperature reached 0° C., a solid began to crystallize from the reaction mixture. Stirring at 20° C. was continued for 1 h then toluene (20 mL) and 40-60 petroleum ether (20 mL) were added slowly and stirring continued for 0.2 h. The resulting colourless solid was collected by filtration to give the title compound (8.0 g, 83%). 1H NMR (Me-d3-OD): 8.81 (1H, s), 8.31 (1H, s), 7.39-7.29 (2H, m), 7.16-7.04 (2H, m), 4.45 (2H, s), 4.19 (4H, s), 1.58 (6H, s). MS: [M+H]+=333.

Workup

additionwas added, steadily over 0.2 h
customA clear solution resulted
customreached 0° C.
customto crystallize from the reaction mixture
additiontoluene (20 mL) and 40-60 petroleum ether (20 mL) were added slowly
stirringstirring
waitcontinued for 0.2 h
filtrationThe resulting colourless solid was collected by filtration

Sources & evidence

ORD record: ord-2707ff214ca54eeea230c98b346e7151
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018214B2

Reaction notes

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