Benzene, 1-bromo-2-(trifluoromethyl)- → HCID 66997586, compound

HRID 2363632Notes

Reaction equation

HRID 2363632 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.Br[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[C:24]([F:27])([F:26])[F:25].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C(O)(CC)(C)C.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:25][C:24]([F:27])([F:26])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[N:2]1[CH2:3][C@@H:4]2[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]2[CH2:1]1

Participants

8

Reactant 4

HCID 9806Benzene, 1-bromo-2-(trifluoromethyl)-HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 51723436tert-Butyl ((1S,5R,6S)-3-azabicyclo[3.3.0]octan-6-yl)carbamate

Product 1

HCID 66997586HCID 66997586, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 64052-Methyl-2-butanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a microwave vial under nitrogen was added tert-butyl(3aR,4S,6aS)-octahydrocyclopenta[c]pyrrol-4-ylcarbamate from Example 216 step B (290 mg, 1.281 mmol), 1-bromo-2-(trifluoromethyl)benzene (0.183 mL, 1.345 mmol), potassium phosphate, tribasic (446 mg, 2.56 mmol), tris(dibenzylideneacetone)dipalladium(0) (23.47 mg, 0.026 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-PHOS, 48.9 mg, 0.103 mmol) in t-amyl alcohol (2.0 mL). The reaction was heated at 80° C. for 18 hours. The reaction was diluted with ethyl acetate (35 mL) and quenched with water (75 mL). The organic phase was removed, and the aqueous layer extracted with 50 mL of ethyl acetate. The solvent was removed in vacuo. The crude material was applied to a 24 g silica gel cartridge with ether and purified using 1-50% ethyl acetate/hexanes to give tert-butyl (3aR,4S,6aS)-2-(2-(trifluoromethyl)phenyl)octahydrocyclopenta[c]pyrrol-4-ylcarbamate: 1H NMR (400 MHz, pyridine-d5) δ ppm 7.66 (d, J=7.8, 1H), 7.45 (t, J=7.6, 1H), 7.25 (d, J=8.1, 1H), 7.11 (t, J=7.5, 1H), 4.21 (s, 1H), 3.40 (d, J=9.1, 1H), 3.11 (dd, J=9.1, 6.9, 1H), 3.03-2.88 (m, 2H), 2.69 (d, J=11.5, 2H), 2.17 (dt, J=11.4, 5.7, 1H), 2.04-1.91 (m, 1H), 1.67 (dd, J=18.5, 7.9, 1H), 1.60-1.46 (m, 11H); MS (ESI+) m/z 371 (M+H)+.

Workup

  1. customquenched with water (75 mL)
  2. customThe organic phase was removed
  3. extractionthe aqueous layer extracted with 50 mL of ethyl acetate
  4. customThe solvent was removed in vacuo
  5. custompurified

Sources & evidence

ORD record
ord-c19e7bc5821b474e85c64795388a373d
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

Loading…