Potassium tert-butoxide → N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-(spiro[3.5]nonan-7-ylmethoxy)benzamide

HRID 1849604Notes

Reaction equation

HRID 1849604 reaction equation
[CH2:1]1[C:4]2([CH2:9][CH2:8][CH:7]([CH2:10][OH:11])[CH2:6][CH2:5]2)[CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[N:18]1([S:22]([NH:25][C:26](=[O:36])[C:27]2[CH:32]=[C:31]([Cl:33])[C:30](F)=[CH:29][C:28]=2[F:35])(=[O:24])=[O:23])[CH2:21][CH2:20][CH2:19]1>CS(C)=O>[N:18]1([S:22]([NH:25][C:26](=[O:36])[C:27]2[CH:32]=[C:31]([Cl:33])[C:30]([O:11][CH2:10][CH:7]3[CH2:6][CH2:5][C:4]4([CH2:1][CH2:2][CH2:3]4)[CH2:9][CH2:8]3)=[CH:29][C:28]=2[F:35])(=[O:24])=[O:23])[CH2:21][CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 53487452Spiro[3.5]nonan-7-ylmethanolHCID 72548904N-(azetidin-1-ylsulfonyl)-5-chloro-2,4-difluorobenzamide

Product 1

HCID 86703459N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-(spiro[3.5]nonan-7-ylmethoxy)benzamideYield 36%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of spiro[3.5]nonan-7-ylmethanol (0.58 g, 3.76 mmol) in anhydrous dimethyl sulfoxide (20 mL) was added potassium t-butoxide (1.05 g, 9.35 mmol) at ambient temperature. After stirring at ambient temperature for 30 minutes, N-(azetidin-1-ylsulfonyl)-5-chloro-2,4-difluorobenzamide (1.17 g, 3.76 mmol) was added to the reaction mixture; stirring was continued at ambient temperature for 2 hours. The mixture was cooled to 0° C. and quenched with 5% aqueous hydrochloride acid (10 mL) followed by extraction with ethyl acetate (100 mL). The organic layer was washed with water (2×40 mL) and brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo, the crude product was purified by silica gel column chromatography using 10-40% ethyl acetate (containing 0.2% acetic acid) in hexanes to afford the title compound as a colorless solid (0.60 g, 36%): 1H NMR (300 MHz, CDCl3) δ 8.60 (d, J=15.6 Hz, 1H), 8.10 (d, J=8.4 Hz, 1H), 6.66 (d, J=13.8 Hz, 1H), 4.23 (t, J=7.8 Hz, 4H), 3.82 (d, J=6.3 Hz, 2H), 2.32-2.20 (m, 2H), 1.88-1.66 (m, 11H), 1.35-1.24 (m, 2H), 1.18-1.05 (m, 2H); MS (ES+) m/z 445.1, 447.1 (M+1), MS (ES−) m/z 443.2, 445.2 (M−1).

Workup

  1. stirringstirring
  2. waitwas continued at ambient temperature for 2 hours
  3. temperatureThe mixture was cooled to 0° C.
  4. customquenched with 5% aqueous hydrochloride acid (10 mL)
  5. extractionfollowed by extraction with ethyl acetate (100 mL)
  6. washThe organic layer was washed with water (2×40 mL) and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-c261f7b35d9e44c6b5a0c65822381d0c
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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