Hydrochloric Acid → N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-(spiro[2.5]octan-1-ylmethoxy)benzamide

HRID 1849611Notes

Reaction equation

HRID 1849611 reaction equation
[CH:1]1([CH2:9][OH:10])[C:3]2([CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]2)[CH2:2]1.CC(C)([O-])C.[K+].[N:17]1([S:21]([NH:24][C:25](=[O:35])[C:26]2[CH:31]=[C:30]([Cl:32])[C:29](F)=[CH:28][C:27]=2[F:34])(=[O:23])=[O:22])[CH2:20][CH2:19][CH2:18]1.Cl>CS(C)=O>[N:17]1([S:21]([NH:24][C:25](=[O:35])[C:26]2[CH:31]=[C:30]([Cl:32])[C:29]([O:10][CH2:9][CH:1]3[C:3]4([CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]4)[CH2:2]3)=[CH:28][C:27]=2[F:34])(=[O:23])=[O:22])[CH2:20][CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 72548904N-(azetidin-1-ylsulfonyl)-5-chloro-2,4-difluorobenzamideHCID 81358403{Spiro[2.5]octan-1-yl}methanol

Product 1

HCID 86703467N-(azetidin-1-ylsulfonyl)-5-chloro-2-fluoro-4-(spiro[2.5]octan-1-ylmethoxy)benzamideYield 39.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of spiro[2.5]octan-1-ylmethanol (prepared according to Huang and Forsyth, Tetrahedron 1997, 53, 16341) (0.40 g, 2.87 mmol) in anhydrous dimethylsulfoxide (5 mL) was added potassium tert-butoxide (0.81 g, 7.24 mmol) and the reaction mixture was stirred for 30 minutes at ambient temperature. To this reaction mixture was added N-(azetidin-1-ylsulfonyl)-5-chloro-2,4-difluorobenzamide (0.90 g, 2.89 mmol) and stirred for 2 hours. The mixture was poured into 1 M aqueous hydrochloric acid, the layers were separated and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water and brine; dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was purified by column chromatography (0% to 30% ethyl acetate in hexanes) to afford the title compound (0.49 g, 39%): 1H NMR (300 MHz, DMSO-d6) δ 11.81 (br s, 1H), 7.78 (d, J=7.5 Hz, 1H), 7.26 (d, J=12.5 Hz, 1H), 4.35-4.31 (dd, J=10.9, 6.3 Hz, 1H), 4.04 (t, J=7.7 Hz, 5H), 2.17 (q, J=7.7 Hz, 2H), 1.77-0.94 (m, 11H), 0.57-0.55 (dd, J=8.5, 4.3 Hz, 1H), 0.30 (t, J=4.7 Hz, 1H); MS (ES−) m/z 429.20 (M−1).

Workup

  1. stirringstirred for 2 hours
  2. customthe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (0% to 30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-82d2b4c6b7f6418ca06511dbb32b2add
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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