Triethylamine → 4-chloro-N-(2,5-difluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide

HRID 1011529ノート

反応式

HRID 1011529 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:20][C:21]2[CH:26]=[C:25]([F:27])[C:24]([C:28]#[N:29])=[CH:23][C:22]=2[F:30])[C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[CH2:18][OH:19])(=[O:10])=[O:9])=[CH:4][CH:3]=1.Cl.N[OH:33].C([N:36]([CH2:39]C)CC)C>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]([CH2:20][C:21]2[CH:26]=[C:25]([F:27])[C:24]([C:28]3[N:36]=[CH:39][O:33][N:29]=3)=[CH:23][C:22]=2[F:30])[C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[CH2:18][OH:19])(=[O:10])=[O:9])=[CH:6][CH:7]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 594977814-chloro-N-(4-cyano-2,5-difluorobenzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide

生成物 1

HCID 468980974-chloro-N-(2,5-difluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide収率 71.7%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

A mixture of 4-chloro-N-(4-cyano-2,5-difluorobenzyl)-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (320 mg, 0.70 mmol) (Example 25), hydroxylamine hydrochloride (247 mg, 3.5 mmol), and triethylamine (488 uL, 3.5 mmol) was refluxed in 8 mL ethanol for 3 h. The reaction was concentrated and the residue was partitioned between ethyl acetate and sat. sodium bicarbonate solution. The organic layer was dried over magnesium sulfate and concentrated. The crude intermediate was stirred in 5 mL triethylorthoformate with three drops of boron trifluoride etherate at room temperature overnight. The reaction was purified by flash chromatography on silica gel with 0 to 60% ethyl acetate in hexane to yield 4-chloro-N-(2,5-difluoro-4-(1,2,4-oxadiazol-3-yl)benzyl)-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (250 mg, 71%). 1H NMR (400 MHz, CDCl3) δ ppm 8.81 (s, 1H), 7.70-7.79 (m, 3H), 7.58 (dd, J=10.20, 5.92 Hz, 1H), 7.50 (d, J=8.56 Hz, 2H), 4.54 (d, J=15.60 Hz, 1H), 4.41 (d, J=15.60 Hz, 1H), 3.64 (td, J=7.93, 3.78 Hz, 2H), 3.14 (t, J=10.58 Hz, 1H), 2.52 (br. s., 1H), 1.58-1.74 (m, 3H), 1.45-1.53 (m, 2H), 1.02-1.26 (m, 4H). Analytical HPLC R.T.=22.92 min. MS [M+H]+=498. HRMS [M+H] calc'd 498.1066, found 498.1087. Chiral LC: R.T.=9.84 min., 99% ee. Optical rotation: [α]=−36.66°, CHCl3 (c=4.29 mg/mL).

後処理

  1. concentrationThe reaction was concentrated
  2. customthe residue was partitioned between ethyl acetate and sat. sodium bicarbonate solution
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe reaction was purified by flash chromatography on silica gel with 0 to 60% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-7d15dfc2fcc742aa9a8a92158109d188
出典データセット
uspto-grants-2011_07
特許番号
US07977362B2

反応ノート

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