Potassium Carbonate → 3-(2-Chloro-4-trifluoromethylphenyl)-7-methoxy-4-(4-(2-pyrrolidin-1-yl-ethoxy)-benzyl)-chromen-2-one

HRID 1167814Notes

Reaction equation

HRID 1167814 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12]1[C:13](=[O:32])[O:14][C:15]2[C:20]([C:21]=1[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1)=[CH:19][CH:18]=[C:17]([O:30][CH3:31])[CH:16]=2.Cl.Cl[CH2:35][CH2:36][N:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1.C([O-])([O-])=O.[K+].[K+].[2H]C(Cl)(Cl)Cl.O>CCO.O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:9])[F:11])[CH:5]=[CH:4][C:3]=1[C:12]1[C:13](=[O:32])[O:14][C:15]2[C:20]([C:21]=1[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH2:35][CH2:36][N:37]3[CH2:41][CH2:40][CH2:39][CH2:38]3)=[CH:25][CH:24]=1)=[CH:19][CH:18]=[C:17]([O:30][CH3:31])[CH:16]=2

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 120881863-(2-Chloro-4-trifluoromethylphenyl)-4-(4-hydroxybenzyl)-7-methoxychromen-2-oneHCID 131724070CHCl3-H2O

Product 1

HCID 120881873-(2-Chloro-4-trifluoromethylphenyl)-7-methoxy-4-(4-(2-pyrrolidin-1-yl-ethoxy)-benzyl)-chromen-2-one

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of 3-(2-chloro-4-trifluoromethylphenyl)-4-(4-hydroxybenzyl)-7-methoxychromen-2-one (460 mg, 1 mmol), 1-(2-chloroethyl)pyrrolidine hydrochloride (254.7 mg, 1.5 mmol) and K2CO3 (413.9 mg, 2.99 mmol) in EtOH (5 mL) was stirred for 2 min prior to the addition of H2O (0.5 mL). The mixture was stirred at 55° C. for 2.5 h, after which time it was cooled to r.t. and poured into CHCl3—H2O. The layers were separated and the aqueous phase was extracted with CHCl3 (3×). The combined organic layers were washed with brine, dried (MgSO4) and the solvent was removed in vacuo. The resultant brown foam was purified using flash chromatography (silica gel, 19:1 CH2Cl2:MeOH) to provide the title compound as a pale brown foam which displayed: 1H NMR (300 MHz, CD3OD) δ 7.83 (s, 1H), 7.65 (d, 1H, J=9.0 Hz), 7.63 (d, 1H, J=8.0 Hz), 7.51 (d, 1H, J=8.0 Hz), 7.00 (d, 1H, J=2.5 Hz), 6.95 (d, 2H, J=8.5 Hz), 6.89 (dd, 1H, J=2.5, 9.0 Hz), 6.79 (d, 2H, J=8.5 Hz),), 4.07 (d, 1H, J=15.5 Hz), 4.05 (t, 2H, J=5.5 Hz), 3.90 (s, 3H), 3.83 (d, 1H, J=15.5 Hz), 2.89 (t, 2H, J=5.5 Hz), 2.72-2.60 (m, 4H), 1.90-1.75 (m, 4H). MS (ESI) m/z 558 (M+H)+.

Workup

  1. stirringThe mixture was stirred at 55° C. for 2.5 h
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted with CHCl3 (3×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent was removed in vacuo
  7. customThe resultant brown foam was purified

Sources & evidence

ORD record
ord-a153816856f34b61b730736038ffd68c
Source dataset
uspto-grants-2003_09
Patent number
US06620838B1

Reaction notes

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