Toluene → 3-[(3-Phenoxyphenyl) [[2'-(trifluoromethyl)[1,1'-biphenyl]-3-yl]methyl]amino]-1,1,1-trifluoro-2-propanol

HRID 1282558Notes

Reaction equation

HRID 1282558 reaction equation
C1(C)C=CC=CC=1.[O:8]([C:15]1[CH:16]=[C:17]([N:21]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32](Br)[CH:31]=2)[CH2:22][CH:23]([OH:28])[C:24]([F:27])([F:26])[F:25])[CH:18]=[CH:19][CH:20]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[F:37][C:38]([F:49])([F:48])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.CN(C=O)C>[O:8]([C:15]1[CH:16]=[C:17]([N:21]([CH2:29][C:30]2[CH:31]=[C:32]([C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=3[C:38]([F:49])([F:48])[F:37])[CH:33]=[CH:34][CH:35]=2)[CH2:22][CH:23]([OH:28])[C:24]([F:27])([F:26])[F:25])[CH:18]=[CH:19][CH:20]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

9

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 110596773-[(3-Phenoxyphenyl)[[3-bromophenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

Product 1

HCID 235060473-[(3-Phenoxyphenyl) [[2'-(trifluoromethyl)[1,1'-biphenyl]-3-yl]methyl]amino]-1,1,1-trifluoro-2-propanol

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent2×HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a toluene (8 mL) solution of 3-[(3-phenoxyphenyl)[[3-bromophenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol (0.51 g, 1.1 mmol) from EX-595B was added 2-(tri-fluoromethyl)phenylboronic acid (0.33 g, 1.7 mmol) and DMF (3 mL). To the resulting solution was added K2CO3 (0.31 g, 2.2 mmol) and Pd(PPh3)4 (0.060 g, 0.05 mmol). The slurry was heated to reflux under argon for 18 h. The cooled mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4) and evaporated to an oil. Purification by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane gave an oil which was dissolved in EtOH, stripped and dried in vacuo to give 0.32 g (55%) of the desired 3-[(3-phenoxyphenyl)[[(2′-(trifluoromethyl)[1,140 -biphenyl]-3-yl]methyl]amino]-1,1,1-tri-fluoro-2-propanol product as a colorless oil. Anal. calcd. for C29H23NO2F6.0.8 EtOH: C, 64.67; H, 4.93; N, 2.46. Found: C, 64.53; H, 4.69; N, 2.49. HRMS calcd. 532.1711 [M+H]+, found: 532.1708. 1H NMR (C6D6) δ1.72 (d, 1H), 3.17 (dd, 1H), 3.46 (dd, 1H), 3.72 (m, 1H), 4.23 (s, 2H), 6.33 (dd, 1H), 6.43 (dd, 1H), 6.52 (t, 1H) 6.82 (m, 2H), 6.9-7.1 (m, 11H), 7.43 (d, 1H).

Workup

  1. temperatureThe slurry was heated
  2. temperatureto reflux under argon for 18 h
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated to an oil
  7. customPurification by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane
  8. customgave an oil which
  9. customdried in vacuo
  10. customto give 0.32 g (55%) of the

Sources & evidence

ORD record
ord-6fbcf53bc011432490b453fc96aa5838
Source dataset
uspto-grants-2002_09
Patent number
US06455519B1

Reaction notes

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