Tricyclo(3.3.1.1'3,7)dec-1-ylmethanol → 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamide

HRID 1427805Notes

Reaction equation

HRID 1427805 reaction equation
[C:1]12([CH2:11][OH:12])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.CC(C)([O-])C.[K+].[Cl:19][C:20]1[C:21](F)=[CH:22][C:23]([F:33])=[C:24]([CH:32]=1)[C:25]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])=[O:26]>CS(C)=O>[C:1]12([CH2:11][O:12][C:21]3[C:20]([Cl:19])=[CH:32][C:24]([C:25]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])=[O:26])=[C:23]([F:33])[CH:22]=3)[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2

Participants

5

Reactant 3

HCID 64556Tricyclo(3.3.1.1'3,7)dec-1-ylmethanolHCID 23665647Potassium tert-butoxideHCID 580424175-chloro-2,4-difluoro-N-(methylsulfonyl)benzamide

Product 1

HCID 725456694-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(methylsulfonyl)benzamideYield 46.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of adamantan-1-ylmethanol (1.00 g, 6.0 mmol) in anhydrous dimethyl sulfoxide (40 mL) was added potassium t-butoxide (1.68 g, 15.0 mmol) at room temperature. The resulting mixture was stirred at room temperature for 30 min followed by the addition of 5-chloro-2,4-difluoro-N-(methylsulfonyl)benzamide (1.62 g, 6.0 mmol). The reaction mixture was stirred at room temperature for 16 h. The mixture was cooled to 0° C. and quenched with hydrochloride acid (1N, 30 mL) followed by extraction with ethyl acetate (200 mL). The organic layer was washed with water (2×40 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo, the crude product was purified by silica gel column chromatography using 10-60% ethyl acetate (containing 0.2% acetic acid) in hexanes as an eluent to afford the title compound as a white solid (1.17 g, 46%): 1H NMR (300 MHz, DMSO-d6) δ 12.10 (s, 1H), 7.77 (d, J=7.5 Hz 1H), 7.23 (d, J=12.5 Hz, 1H), 3.72 (s, 2H), 3.35 (s, 3H), 1.99 (br s, 3H), 1.75-1.64 (m, 12H); 13C NMR (75 MHz, DMSO-d6) δ 162.3 (d, J=2.2 Hz), 159.8 (d, JC-F=255 Hz), 158.3 (d, JC-F=11 Hz), 130.6 (d, JC-F=4 Hz), 116.8 (d, JC-F=3 Hz), 113.6 (d, JC-F=14 Hz), 102.7 (d, JC-F=28 Hz), 79.1, 41.2, 38.5, 36.4, 33.4, 27.3; MS (ES−) m/z 414.1, 416.1 (M−1).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 16 h
  2. temperatureThe mixture was cooled to 0° C.
  3. customquenched with hydrochloride acid (1N, 30 mL)
  4. extractionfollowed by extraction with ethyl acetate (200 mL)
  5. washThe organic layer was washed with water (2×40 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3cacb5cc477d4d1ea55594852bdd3c0a
Source dataset
uspto-grants-2015_01
Patent number
US08933236B2

Reaction notes

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