Phosphorus oxide (P4O10) → 8-fluoro-7-trifluoromethyl-3,4-dihydro-2H-isoquinolin-1-one

HRID 1843950Notes

Reaction equation

C([O:3][C:4](=O)[NH:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[C:10]([F:18])[CH:9]=1)C.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.O=P(Cl)(Cl)Cl>>[F:18][C:10]1[C:11]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:13]=[C:8]2[C:9]=1[C:4](=[O:3])[NH:5][CH2:6][CH2:7]2

Participants

Reactant 3

HCID 14812Phosphorus oxide (P4O10)

HCID 24813Phosphorus oxychloride

HCID 89964249[2-(3-Fluoro-4-trifluoromethyl-phenyl)-ethyl]-carbamic acid ethyl ester

Product 1

HCID 668020098-fluoro-7-trifluoromethyl-3,4-dihydro-2H-isoquinolin-1-oneYield 27.97%

Conditions

Temperature: 110 °C

Procedure

[2-(3-Fluoro-4-trifluoromethyl-phenyl)-ethyl]-carbamic acid ethyl ester (I-47c: 1.5 g, 5.376 mmol) was reacted with P2O5 (1.52 g, 10.75 mmol) and POCl3 (15 mL). The resulting mixture was refluxed for 1 hour at 110° C. to afford the crude product. Purification by column chromatography on silica gel (50% ethylacetate in hexane) afforded 350 mg of the product (27.97% yield).

Workup

customto afford the crude product
customPurification by column chromatography on silica gel (50% ethylacetate in hexane)

Sources & evidence

ORD record: ord-e4cdb16cfa9041a28a0e012966d6fdc9
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946260B2

Reaction notes

Loading…