ethyl 2-(pyrrolidin-2-yl)acetate hydrochloride synthesis

Yield:1251923-73-5 6.38 g

Reaction Conditions:

Stage #1: t-butyl 5-(ethoxycarbonyl)pent-4-enylcarbamatewith trifluoroacetic acid in dichloromethane at 0 - 20; for 24 h;
Stage #2: with triethylamine in dichloromethane at 0 - 20; for 18 h;
Stage #3: with hydrogenchloride in 1,4-dioxane;diethyl ether; for 0.5 h;

Steps:

Intermediate 94: Ethyl pyrrolidin-2-ylacetate hydrochloride

Intermediate 94: Ethyl pyrrolidin-2-ylacetate hydrochlorideTFA (30mL) was added slowly to a solution of ethyl 6-Qert- butoxycarbonylamino)hex-2-enoate (Intermediate 95, 10.25g) in DCM (100mL) at 0°C. The solution was allowed to warm to room temperature and stirred for 24 hours. The mixture wasconcentrated in vacuo and the residue was azeotroped with toluene and DCM. The residue was dissolved in DCM (100mL) and cooled to 0°C. Triethylamine (27mL) was added and the mixture was allowed to warm to room temperature and stirred for 18 hours. The volatiles were removed in vacuo and the residue was dissolved in diethyl ether (200mL) and treated with 4M HC1 in dioxane (4OmL). The mixture was stirred for 30 minutes then evaporated to dryness togive ethyl pyrrolidin-2-ylacetate hydrochloride (6.38g).j00621j ‘H NMR (CDC13) ?: 9.72 (2H, br d), 4.18 (2H, q), 4.01-3.83 (1H, m), 3.48-3.34(2H, m), 3.26-3.14 (1H, m), 2.92-2.78 (1H, m), 2.38-2.20 (1H, m), 2.18-1.95 (2H, m), 1.85-1.67 (1H, m), 1.27 (3H, t).

References:

WO2014/71369,2014,A1 Location in patent:Paragraph 00619-00621