Sodium Hydroxide → 3-(2-Chloro-4-trifluoromethylphenyl)-7-hydroxy-4-(4-(2-pyrrolidin-1-YL-ethoxy)-benzyl)-chromen-2-one

HRID 1167815Notes

Reaction equation

HRID 1167815 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:39])[O:14][C:15]2[C:20]([C:21]=1[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=[CH:25][CH:24]=1)=[CH:19][CH:18]=[C:17]([O:37]C)[CH:16]=2.[OH-].[Na+]>CC(O)=O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:5]=[CH:4][C:3]=1[C:12]1[C:13](=[O:39])[O:14][C:15]2[C:20]([C:21]=1[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][N:32]3[CH2:33][CH2:34][CH2:35][CH2:36]3)=[CH:25][CH:24]=1)=[CH:19][CH:18]=[C:17]([OH:37])[CH:16]=2

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 120881873-(2-Chloro-4-trifluoromethylphenyl)-7-methoxy-4-(4-(2-pyrrolidin-1-yl-ethoxy)-benzyl)-chromen-2-one

Product 1

HCID 101749503-(2-Chloro-4-trifluoromethylphenyl)-7-hydroxy-4-(4-(2-pyrrolidin-1-YL-ethoxy)-benzyl)-chromen-2-one

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
130 °C

Procedure

3-(2-Chloro-4-trifluoromethylphenyl)-7-methoxy-4-(4-(2-pyrrolidin-1-yl-ethoxy)-benzyl)-chromen-2-one (330 mg, 0.59 mmol) was dissolved in AcOH (2.4 mL)-48% aq HBr (2.4 mL). The mixture was stirred at 130° C. for 15 h. After cooling the mixture to r.t., it was poured onto EtOAc/aq NaHCO3. 1M aq NaOH was then added to bring the pH to 8. The layers were separated and the aqueous layer was back-extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (MgSO4) and the solvent was removed in vacuo. The residue was purified using flash chromatography (silica gel, 5:1 CH2Cl2-MeOH) to provide the title compound as a yellow foam showing: IR (KBr) v=3670-2140, 1709, 1611, 1569, 1511, 1367, 1323, 1247, 1172, 1133, 1081, 1067, 1044, 1012 cm−1. 1H NMR (400 MHz, CD3OD) δ 7.81 (d, 1H, J=1.5 Hz), 7.61 (dd, 1H, J=1.5, 8.0 Hz), 7.56 (d, 1H, J=8.8 Hz), 7.48 (d, 1H, J=8.0 Hz), 6.93 (d, 2H, J=8.5 Hz), 6.79 (d, 2H), J=8.5 Hz), 6.76 (d, 1H, J=2.5 Hz), 6.73 (dd, 1H, J=2.5, 8.8 Hz), 4.09 (t, 2H, J=5.5 Hz), 4.05 (d, 1H, J=15.5 Hz), 3.80 (d, 1H, J=15.5 Hz), 3.04 (t, 2H, J=5.5 Hz), 2.86-2.78 (m, 4H), 1.92-1.82 (m, 4H). HRMS (ESI) calcd for C29H25ClF3NO4 (M+H)+: 544.1502; found 544.1504.

Workup

  1. temperatureAfter cooling the mixture to r.t.
  2. additionit was poured onto EtOAc/aq NaHCO3
  3. customThe layers were separated
  4. extractionthe aqueous layer was back-extracted with EtOAc (3×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent was removed in vacuo
  8. customThe residue was purified

Sources & evidence

ORD record
ord-bb8c66484b1345e99d4829d4fbf7188a
Source dataset
uspto-grants-2003_09
Patent number
US06620838B1

Reaction notes

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