Methanol → (4R,5R)-5-(3-Fluorophenyl)-4-(2-methoxy-5-(phenylethynyl)pyridin-3-yl)oxazolidin-2-one

HRID 2362458Notes

Reaction equation

HRID 2362458 reaction equation
F[C:2]1[C:7]([C@@H:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=3)[O:11][C:10](=[O:20])[NH:9]2)=[CH:6][C:5]([C:21]#[C:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:4][N:3]=1.[OH-:29].[K+].[CH3:31]O>>[F:19][C:15]1[CH:14]=[C:13]([C@H:12]2[O:11][C:10](=[O:20])[NH:9][C@@H:8]2[C:7]2[C:2]([O:29][CH3:31])=[N:3][CH:4]=[C:5]([C:21]#[C:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:6]=2)[CH:18]=[CH:17][CH:16]=1

Participants

4

Reactant 3

HCID 887Methanol2×HCID 14797Potassium HydroxideHCID 69084163(4R,5R)-4-(2-Fluoro-5-(phenylethynyl)pyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one

Product 1

HCID 69086137(4R,5R)-5-(3-Fluorophenyl)-4-(2-methoxy-5-(phenylethynyl)pyridin-3-yl)oxazolidin-2-one

Procedure

To a solution of (4R,5R)-4-(2-fluoro-5-(phenylethynyl)pyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one (10 mg, 0.027 mmol) in methanol (0.25 mL) at 0° C. was added a solution of potassium hydroxide (14.9 mg, 0.266 mmol) in methanol (0.25 mL, 6.18 mmol). After 1 h at 0° C., the reaction was allowed to stir at room temperature for 24 h. The reaction was quenched by addition of solid ammonium chloride (30 mg) and concentrated. The resulting residue was dissolved in dichloromethane, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, and concentrated. The product was purified by Prep HPLC (TFA/MeOH, sunfire column) and concentrated to give 7.7 mg (73%). 1H NMR (CDCl3) δ: 8.38 (d, J=2.1 Hz, 1H), 7.84-7.88 (m, 1H), 7.53-7.58 (m, 2H), 7.43 (td, J=7.9, 5.8 Hz, 1H), 7.36-7.40 (m, 3H), 7.24 (dd, J=7.6, 0.6 Hz, 1H), 7.19 (dt, J=9.4, 2.0 Hz, 1H), 7.09-7.15 (m, 1H), 5.90 (s, 1H), 5.37 (d, J=4.3 Hz, 1H), 4.98 (d, J=4.3 Hz, 1H), 4.00 (s, 3H). 13C NMR (CDCl3) δ: 163.1, 160.1, 158.8, 150.1, 141.1, 137.8, 131.7, 130.7, 128.7, 128.6, 122.7, 121.4, 121.1, 121.1, 116.0, 114.1, 112.8, 91.8, 85.4, 83.1, 58.6, 54.1. Mass spec.: 389.2 (MH)+.

Workup

  1. customThe reaction was quenched by addition of solid ammonium chloride (30 mg)
  2. concentrationconcentrated
  3. dissolutionThe resulting residue was dissolved in dichloromethane
  4. additiondiluted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe product was purified by Prep HPLC (TFA/MeOH, sunfire column)
  9. concentrationconcentrated
  10. customto give 7.7 mg (73%)

Sources & evidence

ORD record
ord-fafa790547b4458fb959e3979f092fc2
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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