Hydrogen Bromide → 2,2-Difluoro-1-phenyl-1,2,3,6,7,8,9,10-octahydro-8-aza-cyclohepta[e]indene

HRID 925208Notes

Reaction equation

C(OC([N:6]1[CH2:27][CH2:26][C:10]2[C:11]3[CH:12]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:13]([F:19])([F:18])[CH2:14][C:15]=3[CH:16]=[CH:17][C:9]=2[CH2:8][CH2:7]1)=O)C.Br>C(O)(=O)C>[F:19][C:13]1([F:18])[CH:12]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:11]2[C:10]3[CH2:26][CH2:27][NH:6][CH2:7][CH2:8][C:9]=3[CH:17]=[CH:16][C:15]=2[CH2:14]1

Participants

Conditions

Temperature: 60 °C

Procedure

Into a 250 ml flask, the product from step (e) (3.75 g, 10.10 mmol) dissolved in acetic acid (50 ml) and HBr (33% in acetic acid, 50 ml) was added. The reaction mixture was heated to 60° C. for 6 hours. The reaction mixture was cooled and the volatiles were evaporated in vacuo. The crude product was dissolved in water (100 ml) and washed with diethyl ether (3×). The aqueous layer was basified with 2M NaOH to pH 10 and then extracted with DCM (3×). The combined DCM extracts were washed with brine, dried over Na2SO4, and solvent evaporated in vacuo to give the title compound as tan oil (2.8 g) which solidified over time. 1H NMR (300 MHz, CDCl3) δ 7.32-7.26 (m, 3H); 7.10-7.07 (m, 2H); 7.02-6.99 (m, 2H); 4.62 (d, J=19.8 Hz, 1H); 3.44-3.35 (m, 2H); 2.99-2.83 (m, 4H); 2.73-2.64 (m, 2H); 2.58-2.45 (m, 2H); 2.33 (bs, 1H); MS: ESI (positive): 300 (M+1).

Workup

temperatureThe reaction mixture was cooled
customthe volatiles were evaporated in vacuo
dissolutionThe crude product was dissolved in water (100 ml)
washwashed with diethyl ether (3×)
extractionextracted with DCM (3×)
washThe combined DCM extracts were washed with brine
dry with materialdried over Na2SO4, and solvent
customevaporated in vacuo

Sources & evidence

ORD record: ord-75d5265831bd43999cc42d5da12523b8
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284277B2

Reaction notes

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