HCID 89634498, compound → HCID 71609990, compound

HRID 717510Notes

Reaction equation

HRID 717510 reaction equation
[F:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([C@@H:8]([CH3:48])[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.O>[F:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][N:5]([C@@H:8]([CH3:48])[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]([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 89634498HCID 89634498, compound

Product 1

HCID 71609990HCID 71609990, compoundYield 70.4%

Reagents, catalysts & solvents 1

HCID 21899381Acetic acid--water (1/1)Solvent

Procedure

(3R)-3-(fluoromethyl)-1-((2S)-1-(4-(4-methyl-6-((tetrahydro-2H-pyran-2-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2H-chromen-2-yl)phenoxy)propan-2-yl)pyrrolidine (785 mg, 1.19 mmol) was stirred in 80% acetic acid/H2O (6.0 mL) at room temperature for 2 days. The solvents were removed on a rotary evaporator, and the residue was dissolved in ethyl acetate. The organic layer was washed with sat'd aqueous NaHCO3, washed with water, washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. This crude material was then purified by silica gel chromatography (0-4% MeOH/DCM) to afford 2-(4-((S)-2-((R)-3-(fluoromethyl)pyrrolidin-1-yl)propoxy)phenyl)-3-(3-hydroxyphenyl)-4-methyl-2H-chromen-6-ol (410 mg, 70%) as pale pink solid. 1H NMR (DMSO-d6): δ 9.43 (s, 1H), 8.94 (s, 1H), 7.18 (d, 2H), 7.12 (t, 1H), 6.79 (d, 2H), 6.73 (m, 1H), 6.68 (dt, 1H), 6.65 (m, 1H), 6.61 (m, 1H), 6.49-6.45 (m, 2H), 5.83 (s, 1H), 4.35-4.30 (m, 1H), 4.23-4.18 (m, 1H), 3.99-3.93 (m, 1H), 3.74-3.70 (m, 1H), 2.69-2.60 (m, 2H), 2.58-2.52 (m, 2H), 2.45-2.32 (m, 2H), 2.02 (s, 3H), 1.82-1.75 (m, 1H), 1.36-1.30 (m, 1H), 1.07 (d, 3H); LCMS: 490.2 (M+H)+.

Workup

  1. customThe solvents were removed on a rotary evaporator
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washThe organic layer was washed with sat'd aqueous NaHCO3
  4. washwashed with water
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThis crude material was then purified by silica gel chromatography (0-4% MeOH/DCM)

Sources & evidence

ORD record
ord-d7bf112dffbb46a8a01b7eacc9cf9e36
Source dataset
uspto-grants-2015_11
Patent number
US09193714B2

Reaction notes

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