3-Furanol, tetrahydro- → US10023592, Example 175

HRID 575665Notes

Reaction equation

HRID 575665 reaction equation
[O:1]1[CH2:5][CH2:4][CH:3]([OH:6])[CH2:2]1.[H-].[Na+].F[C:10]1[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][C:11]=1[C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])[N:22]([CH3:31])[CH:21]=1>CN(C=O)C>[CH3:31][N:22]1[CH:21]=[C:20]([C:11]2[CH:12]=[C:13]([S:16]([CH3:19])(=[O:18])=[O:17])[CH:14]=[CH:15][C:10]=2[O:6][CH:3]2[CH2:4][CH2:5][O:1][CH2:2]2)[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]1=[O:30]

Participants

5

Reactant 3

HCID 99603-Furanol, tetrahydro-HCID 24758Sodium hydrideHCID 1180219014-(2-Fluoro-5-methylsulfonylphenyl)-2-methylisoquinolin-1-one

Product 1

HCID 118021912US10023592, Example 175Yield 47%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of oxolan-3-ol (175.0 mg, 1.99 mmol) in anhydrous DMF (3 mL) was added NaH (66.0 mg, 1.65 mmol, 60% in mineral oil) at 0° C. and then stirred at 0° C. for 0.5 hrs. 4-(2-fluoro-5-methylsulfonylphenyl)-2-methylisoquinolin-1-one (110.0 mg, 0.33 mmol) was added. The mixture was stirred at 0° C. for 0.5 h and then at r.t. for 3 hrs. It was then quenched with aqueous sat. NH4Cl (20 mL) and extracted with EA (20 mL×3). The combined organic layers were washed with brine (40 mL), dried over Na2SO4, and concentrated under reduced pressure to afford a crude product which was purified by prep-HPLC to give the title compound (62.0 mg, 39.7%) as a light yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.51 (d, J=7.6 Hz, 1H), 8.00 (dd, J1=8.8 Hz, J2=2.4 Hz, 1H), 7.89 (d, J=2.4 Hz, 1H), 7.58-7.51 (m, 2H), 7.11-7.03 (m, 3H), 5.01-4.98 (m, 1H), 3.97 (dd, J1=10.4 Hz, J2=4.8 Hz, 1H), 3.76-3.70 (m, 2H), 3.67 (s, 3H), 3.61-3.42 (m, 1H), 3.11 (s, 3H), 2.18-1.88 (m, 2H). LCMS (M+H)+=400.0 (M+1)+

Workup

  1. stirringThe mixture was stirred at 0° C. for 0.5 h
  2. waitat r.t. for 3 hrs
  3. customIt was then quenched with aqueous sat. NH4Cl (20 mL)
  4. extractionextracted with EA (20 mL×3)
  5. washThe combined organic layers were washed with brine (40 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto afford a crude product which
  9. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-dbfde99023fe42b8b595e7774e607704
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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