Tetrahydrofuran → HCID 58913087, compound

HRID 1296682Notes

Reaction equation

HRID 1296682 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31]C(=O)C(C)(C)C)=[CH:27][CH:26]=3)=[C:8]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[C:9](=[O:13])[O:10]2)=[CH:5][C:4]=1[CH3:38].O[Li].O.C1COCC1>O>[OH:31][C:28]1[CH:29]=[CH:30][C:25]([CH2:24][C:7]2[C:6]3[C:11](=[CH:12][C:3]([O:2][CH3:1])=[C:4]([CH3:38])[CH:5]=3)[O:10][C:9](=[O:13])[C:8]=2[C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:21])[F:22])=[CH:16][CH:15]=2)=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 58913125HCID 58913125, compound

Product 1

HCID 58913087HCID 58913087, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 2,2-dimethyl-propionic acid 4-(7-methoxy-6-methyl-2-oxo-3-(4-trifluoromethyl-phenyl)-2H-chromen-4-ylmethyl)-phenyl ester (72 mg, 0.14 mmol) and LiOH.H2O (23 mg, 0.55 mmol) in an 8:1 mixture of THF:H2O (4.5 mL) was stirred at 30° C. for 4 h. THF was removed in vacuo and AcOEt was added. The pH of the aqueous layer was lowered to 5 by addition of aqueous 1N HCl. The layers were separated and the aqueous phase was extracted with AcOEt (2×). The combined organic layers were washed with brine, dried (MgSO4) and concentrated. The residue was purified using flash chromatography (99:1 CH2Cl2:MeOH) to provide the desired compound as a beige solid (40 mg, 67%). 1H NMR (300 MHz, CDCl3) δ 7.62 (d, J=8.0 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H), 7.25 (d, J=1.0 Hz, 1H), 6.92–6.86 (m, 2H), 6.82 (s, 1H), 6.75–6.69 (m, 2H), 3.95 (s, 2H), 3.90 (s, 3H), 2.16 (s, 3H); MS (ESI) m/z 440.9 (M+H)+; HPLC tR 6.50 min.

Workup

  1. customTHF was removed in vacuo and AcOEt
  2. additionwas added
  3. additionThe pH of the aqueous layer was lowered to 5 by addition of aqueous 1N HCl
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with AcOEt (2×)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was purified

Sources & evidence

ORD record
ord-6da70bb5004a47269fc99a8606f4f601
Source dataset
uspto-grants-2007_07
Patent number
US07247646B2

Reaction notes

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