Water → HCID 59354862, compound

HRID 1776382Notes

Reaction equation

HRID 1776382 reaction equation
[CH3:1][C:2]1([CH3:41])[O:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([N:13](S(C)(=O)=O)[S:14]([CH3:17])(=[O:16])=[O:15])=[CH:9][CH:8]=2)=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]3[CH:39]=[CH:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]=3)=[CH:24][CH:23]=2)[C:3]1=[O:40].O.[OH-].[Na+]>C1COCC1>[CH3:1][C:2]1([CH3:41])[O:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][S:14]([CH3:17])(=[O:15])=[O:16])=[CH:9][CH:8]=2)=[C:4]([C:22]2[CH:23]=[CH:24][C:25]([O:28][CH2:29][C:30]3[CH:39]=[CH:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]=3)=[CH:26][CH:27]=2)[C:3]1=[O:40]

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 59354786HCID 59354786, compound

Product 1

HCID 59354862HCID 59354862, compoundYield 64.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of N-(4-(5,5-dimethyl-4-oxo-3-(4-(quinolin-2-ylmethoxy)phenyl)-4,5-dihydrofuran-2-yl)phenyl)-N-(methylsulfonyl)methane sulfonamide (40 mg, 0.06 mmol) in THF: H2O (6 mL) was added 2N NaOH (1.0 mL) at 0° C. under N2 atmosphere. The reaction mixture was stirred at 0° C. for 10 min. Upon complete consumption of the starting material (by TLC), the reaction mixture was diluted with water and extracted with EtOAc (2×15 mL). The combined organic layers were washed with water (2×5 mL), brine and dried over anhydrous Na2SO4. After filtration and evaporation, the crude material was purified by silica gel column chromatography to afford N-(4-(5,5-dimethyl-4-oxo-3-(4-(quinolin-2-ylmethoxy)phenyl)-4,5-dihydrofuran-2-yl)phenyl)methane sulfonamide (20 mg, 26%), as a pale yellow solid. 1H NMR (500 MHz, CDCl3): δ 8.45 (d, J=8.5 Hz, 1 H), 8.12 (t, J=7.9 Hz, 1H), 7.78 (t, J=8.4 Hz, 1 H), 7.70 (d, J=8.2 Hz, 1 H), 7.64 (t, J=8.2 Hz, 1 H), 7.44 (d, J=8.5 Hz, 2 H), 7.18 (d, J=7.5 Hz, 2 H), 7.10 (d, J=7.5 Hz, 2 H), 6.98 (d, J=8.2 Hz, 2H), 5.42 (s, 2 H), 2.85 (s, 3 H), 1.44 (s, 6H). MS: [M+Na]: m/z=537.3, [M+H]: m/z=515.2 HPLC: 95.7% (RT-2.37 min), Column: Acquity BEH-C-18, 50×2.1 mm, 1.7 um. Mobile Phase: 0.025% TFA in Water (A), ACN (B), Flow rate: 0.5 ml/min (Gradient).

Workup

  1. customUpon complete consumption of the starting material (by TLC)
  2. additionthe reaction mixture was diluted with water
  3. extractionextracted with EtOAc (2×15 mL)
  4. washThe combined organic layers were washed with water (2×5 mL), brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationAfter filtration and evaporation
  7. customthe crude material was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-469f0797b9bb47ebab732322319eb0e9
Source dataset
uspto-grants-2016_02
Patent number
US09265767B2

Reaction notes

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