Dimethylformamide → cis-8-fluoro-2-propyl-1,3,4,4a, 5,10b-hexahydro-2H-benzo[h]isoquinolin-6-one

HRID 382814Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C@H:14]3[C@H:9]([CH2:10][CH2:11][NH:12][CH2:13]3)[CH2:8][C:7](=[O:15])[C:6]=2[CH:16]=1.Br[CH2:18][CH2:19][CH3:20].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[C@H:14]3[C@H:9]([CH2:10][CH2:11][N:12]([CH2:18][CH2:19][CH3:20])[CH2:13]3)[CH2:8][C:7](=[O:15])[C:6]=2[CH:16]=1

Participants

Conditions

Temperature: 125 °C

Procedure

A mixture of 0.29 g (1.32 mmol) of cis-8-fluoro-1,3,4,4a,5,10b-hexahydro-2H-benzo[h]isoquinolin-6-one, 0.12 ml (1.39 mmol) of bromopropane, 0.2 g (1.45 mmol) of potassium carbonate and 20 ml of anhydrous DMF was heated to 125° C. for 1 hour. Subsequently, the mixture was poured into 3 ml of water and extracted once with 50 ml of ethyl acetate. The organic phase was washed once with 40 ml of saturated sodium chloride solution, dried (MgSO4) and concentrated in a vacuum. The crude product obtained was purified by column chromatography on silica gel (methylene chloride/methanol/NH4OH 9:1:0.2). There were obtained 220 mg (63%) of cis-8-fluoro-2-propyl-1,3,4,4a, 5,10b-hexahydro-2H-benzo[h]isoquinolin-6-one as a yellow oil, which was converted with MeOH/HCl into the hydrochloride with m.p. >220°.

Workup

extractionextracted once with 50 ml of ethyl acetate
washThe organic phase was washed once with 40 ml of saturated sodium chloride solution
dry with materialdried (MgSO4)
concentrationconcentrated in a vacuum
customThe crude product obtained
customwas purified by column chromatography on silica gel (methylene chloride/methanol/NH4OH 9:1:0.2)

Sources & evidence

ORD record: ord-fe96d375b20c48fd8326b4dac1cd99aa
Source dataset: uspto-grants-2001_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06310208B1

Reaction notes

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