1-Chloroethyl chloroformate → 2-Trifluoromethyl-5,6,7,8-tetrahydro-[1,6]naphthyridine-3-carboxylic acid ethyl ester hydrochloride

HRID 132837Notes

Reaction equation

C([N:8]1[CH2:17][CH2:16][C:15]2[N:14]=[C:13]([C:18]([F:21])([F:20])[F:19])[C:12]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:11][C:10]=2[CH2:9]1)C1C=CC=CC=1.[Cl:27]C(OC(Cl)C)=O>ClCCl>[ClH:27].[F:21][C:18]([F:19])([F:20])[C:13]1[C:12]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:11][C:10]2[CH2:9][NH:8][CH2:17][CH2:16][C:15]=2[N:14]=1

Participants

Conditions

Temperature: 45 °C

Procedure

A solution of the product (140 mg, 0.385 mmol) from Step B in 1.5 mL of dry dichloromethane was treated with 1-chloroethyl chloroformate (0.050 mL, 0.46 mmol). The reaction mixture was warmed to 45° C. After 20 h, the solution was cooled to room temperature and concentrated under a stream of nitrogen. The resultant residue was dissolved in 3 mL of methanol and the solution was warmed at 40° C. for 2.5 h. The resultant solution was cooled and concentrated under a stream of nitrogen, and the residue was triturated with 4 mL of ethyl acetate. The solid precipitate was collected and dried in vacuo to afford the title compound as a white crystalline solid. LC/MS 275.0 (M+1).

Workup

temperaturethe solution was cooled to room temperature
concentrationconcentrated under a stream of nitrogen
dissolutionThe resultant residue was dissolved in 3 mL of methanol
temperaturethe solution was warmed at 40° C. for 2.5 h
temperatureThe resultant solution was cooled
concentrationconcentrated under a stream of nitrogen
customthe residue was triturated with 4 mL of ethyl acetate
customThe solid precipitate was collected
customdried in vacuo

Sources & evidence

ORD record: ord-8721b0d3d4184e87adc8175e27d49533
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07388019B2

Reaction notes

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