Sodium Carbonate → [3'-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-yl]-methanol

HRID 1782681Notes

Reaction equation

HRID 1782681 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH2:5][N:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=2)[CH2:9][CH2:8][CH2:7]1.[OH:23][CH2:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C>[F:17][C:16]([F:19])([F:18])[C:13]1[CH:14]=[C:15]2[C:10]([CH2:9][CH2:8][CH2:7][N:6]2[CH2:5][C:4]2[CH:3]=[C:2]([C:28]3[CH:29]=[CH:30][C:25]([CH2:24][OH:23])=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 115958231-(3-Bromo-benzyl)-7-trifluoromethyl-1,2,3,4-tetrahydro-quinoline

Product 1

HCID 11603644[3'-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-yl]-methanol

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Under a nitrogen atmosphere, a solution of 1-(3-bromo-benzyl)-7-trifluoromethyl-1,2,3,4-tetrahydro-quinoline (2.36 g, 6.37 mmol), 4-(hydroxymethyl)phenyl boronic acid (1.07 g, 7.01 mmol), and 2 M Na2CO3 (7 mL, 12.7 mmol) in 16 mL of toluene and 4 mL ethanol (0.3 M) was treated with tetrakistriphenylphosphine palladium (Pd(Ph3)4) (0.37 g, 0.32 mmol) and heated to 80° C. for 2 hours. After cooling to room temperature the solution was extracted with ethyl acetate, dried over MgSO4, and concentrated. Purification by flash chromatography (30% ethyl acetate in heptane) provided [3′-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-yl]-methanol. 1H NMR (CDCl3, 300 MHz) δ 7.49-7.32 (m, 6 H), 7.16-7.13 (m, 2 H), 6.95 (d, J=8.4 Hz, 1 H), 6.73-6.60 (m, 2 H), 4.66 (s, 2 H), 4.48 (s, 2 H), 3.30 (t, J=5.7 Hz, 2 H), 2.76 (t, J=6.3 Hz, 2 H), 1.98-1.90 (m, 2 H); ESI-LCMS m/z calcd for C24H22F3NO: 397.4; found 398.7 (M+1)+.

Workup

  1. temperatureAfter cooling to room temperature the solution
  2. extractionwas extracted with ethyl acetate
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customPurification by flash chromatography (30% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-a49809f6e49547d4830ecc1868c240e0
Source dataset
uspto-grants-2009_03
Patent number
US07498356B2

Reaction notes

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