Benzene, 1-bromo-3-(trifluoromethyl)- → HCID 66997470, compound

HRID 2363623Notes

Reaction equation

HRID 2363623 reaction equation
[CH2:1]1[C@H:5]2[CH2:6][CH2:7][C@H:8]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C@H:4]2[CH2:3][NH:2]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:72]1[CH:77]=[CH:76][CH:75]=[C:74]([C:78]([F:81])([F:80])[F:79])[CH:73]=1>C1(C)C=CC=CC=1>[F:79][C:78]([F:81])([F:80])[C:74]1[CH:73]=[C:72]([N:2]2[CH2:3][C@@H:4]3[C@@H:8]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14])[CH2:7][CH2:6][C@@H:5]3[CH2:1]2)[CH:77]=[CH:76][CH:75]=1

Participants

6

Reactant 4

HCID 9817Benzene, 1-bromo-3-(trifluoromethyl)-HCID 62657Potassium Phosphate, TribasicHCID 634876Binap, (A+-)-HCID 51723436tert-Butyl ((1S,5R,6S)-3-azabicyclo[3.3.0]octan-6-yl)carbamate

Product 1

HCID 66997470HCID 66997470, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl(3aR,4S,6aS)-octahydrocyclopenta[c]pyrrol-4-ylcarbamate from Example 252 Step B (50.3 mg, 0.222 mmol), tris(dibenzylidineacetone)dipalladium(0) (4.07 mg, 4.45 μmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (8.30 mg, 0.013 mmol), potassium phosphate, tribasic (54.2 mg, 0.311 mmol) and 1-bromo-3-(trifluoromethyl)benzene (0.032 mL, 0.233 mmol) were combined in toluene (2 mL) and put under nitrogen. The reaction mixture was heated at 80° C. overnight. The reaction was quenched with water (1 mL), the phases were separated, and the organic phase was applied to a 4 g silica gel cartridge and purified using a gradient of 1-20% ethyl acetate/hexanes over 15 minutes to give tert-butyl(3aR,4S,6aS)-2-(3-(trifluoromethyl)phenyl)octahydrocyclopenta[c]pyrrol-4-ylcarbamate: 1H NMR (400 MHz, pyridine-d5) δ ppm 7.73 (d, J=6.3, 1H), 7.33 (t, J=7.8, 1H), 7.06 (d, J=7.4, 1H), 6.91 (s, 1H), 6.76 (d, J=7.9, 1H), 4.13-4.02 (m, 1H), 3.44 (d, J=10.0, 1H), 3.34-3.27 (m, 1H), 3.21-3.12 (m, 1H), 2.99 (d, J=10.1, 1H), 2.81-2.70 (m, 2H), 2.12 (td, J=12.6, 6.4, 1H), 2.06-1.95 (m, 1H), 1.73 (dq, J=15.0, 7.5, 1H), 1.55 (s, 9H), 1.44-1.34 (m, 1H); MS (ESI+) m/z 371 (M+H)+.

Workup

  1. customThe reaction was quenched with water (1 mL)
  2. customthe phases were separated
  3. custompurified
  4. customover 15 minutes

Sources & evidence

ORD record
ord-3a64dbd669684823b78d3d99d56d6bdb
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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