Benzene, 1-bromo-3-(trifluoromethyl)- → 2,2-Difluoro-1-(3-trifluoromethyl-phenyl)-1,2,3,6,7,8,9,10-octahydro-8-aza-cyclohepta[e]indene

HRID 925209Notes

Reaction equation

HRID 925209 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[C:5]([Mg]Cl)[CH:6]=[CH:7][CH:8]=1.BrC1C=C(C(F)(F)F)C=CC=1.C([Mg]Cl)(C)C.C(OC([N:34]1[CH2:56][CH2:55][C:38]2[C:39]3[C:40](O)(C4C=CC=CC=4)[C:41]([F:47])([F:46])[CH2:42][C:43]=3[CH:44]=[CH:45][C:37]=2[CH2:36][CH2:35]1)=O)C>C1COCC1>[F:47][C:41]1([F:46])[CH:40]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:12])([F:11])[F:1])[CH:4]=2)[C:39]2[C:38]3[CH2:55][CH2:56][NH:34][CH2:35][CH2:36][C:37]=3[CH:45]=[CH:44][C:43]=2[CH2:42]1

Participants

6

Reactant 4

HCID 9817Benzene, 1-bromo-3-(trifluoromethyl)-HCID 867253182,2-Difluoro-1-hydroxy-1-phenyl-1,3,6,7,9,10-hexahydro-2H-8-aza-cyclohepta[e]indene-8-carboxylic acid ethyl esterHCID 178418918HCID 178418918, compoundHCID 178506175HCID 178506175, compound

Product 1

HCID 766843552,2-Difluoro-1-(3-trifluoromethyl-phenyl)-1,2,3,6,7,8,9,10-octahydro-8-aza-cyclohepta[e]indene

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Example 18 was prepared in a similar fashion to Example 14, except (3-(trifluoromethyl)phenyl)magnesium chloride (prepared from 3-bromobenzotrifluoride (1 eq) in THF, followed by addition of isopropyl magnesium chloride (2M in THF, 1 eq) at room temperature and stirring for 16 hours was used instead of phenylmagnesium bromide (example 14, step (c)) 1H NMR (300 MHz, CDCl3) δ 7.55-7.53 (m, 1H); 7.42 (t, J=7.8 Hz, 1H); 7.29 (bs, 1H); 7.20-7.17 (m, 1H); 7.13-7.07 (m, 2H); 4.70 (d, J=19.2, 1H); 3.51-3.36 (m, 2H); 3.01-2.84 (m, 4H); 2.74-2.61 (m, 2H); 2.54-2.49 (m, 2H); 2.01 (bs, 1H); MS: ESI (positive): 368 (M+1).

Sources & evidence

ORD record
ord-942306b90b104e5a85abe7033e6aeebd
Source dataset
uspto-grants-2016_03
Patent number
US09284277B2

Reaction notes

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