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

HRID 1849611ノート

反応式

HRID 1849611 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-82d2b4c6b7f6418ca06511dbb32b2add
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

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