HCID 89634412, compound → HCID 89620108, compound

HRID 717509Notes

Reaction equation

HRID 717509 reaction equation
[F:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[C:26]([C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([O:33]C5CCCCO5)[CH:28]=4)=[C:25]([CH3:40])[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([O:41]C5CCCCO5)[CH:23]=4)[O:18]3)=[CH:13][CH:12]=2)[CH2:4]1>C(O)(=O)C>[F:1][CH2:2][CH:3]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C@@H:17]3[C:26]([C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([OH:33])[CH:28]=4)=[C:25]([CH3:40])[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([OH:41])[CH:23]=4)[O:18]3)=[CH:13][CH:12]=2)[CH2:4]1

Participants

3

Reactant 1

HCID 89634412HCID 89634412, compound

Product 1

HCID 89620108HCID 89620108, compoundYield 79.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of (3R)-3-(fluoromethyl)-1-(2-(4-(4-methyl-6-((tetrahydro-2H-pyran-2-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2H-chromen-2-yl)phenoxy)ethyl)pyrrolidine (1.87 g, 2.9 mmol) in acetic acid (80% aq., 30 mL) was stirred at room temperature overnight. The acetic acid was removed and the residue was partitioned between ethyl acetate and sat'd aqueous NaHCO3. The organic layer was washed with sat'd aqueous NaHCO3, dried over sodium sulfate, filtered and the solvent removed. The residue was purified by flash chromatography on silica gel (0 to 5% methanol/dichloromethane) to afford 1.1 g of (R)-2-(4-(2-(3-(fluoromethyl)pyrrolidin-1-yl)ethoxy)phenyl)-3-(3-hydroxyphenyl)-4-methyl-2H-chromen-6-ol as a pinkish foam. 1H NMR (DMSO-d6): δ 9.43 (s, 1H), 8.94 (s, 1H), 7.18 (d, 2H), 7.14 (t, 1H), 6.78 (d, 2H), 6.73 (s, 1H), 6.67-6.65 (m, 2H), 6.65 (s, 1H), 6.49-6.45 (m, 2H), 5.83 (s, 1H), 4.35-4.30 (m, 1H), 4.23-4.19 (m, 1H), 3.96 (t, 2H), 2.71 (t, 2H), 2.60 (t, 1H), 2.46-2.40 (m, 3H), 2.36-2.31 (m, 1H), 2.02 (s, 3H), 1.83-1.76 (m, 1H), 1.39-1.30 (m, 1H); LCMS: 476 (M+H)+.

Workup

  1. customThe acetic acid was removed
  2. customthe residue was partitioned between ethyl acetate
  3. washThe organic layer was washed with sat'd aqueous NaHCO3
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent removed
  7. customThe residue was purified by flash chromatography on silica gel (0 to 5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-61c0388650cb400da82141f69868c0b5
Source dataset
uspto-grants-2015_11
Patent number
US09193714B2

Reaction notes

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