Lithium hydroxide, monohydrate → [4-(4-Cyclohexylsulfamoyl-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid

HRID 1468437ノート

反応式

HRID 1468437 の反応式
O.[OH-].[Li+].C[O:5][C:6](=[O:36])[CH2:7][C:8]1[C:17]([CH3:18])=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([S:25](=[O:34])(=[O:33])[NH:26][CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)=[CH:21][CH:20]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:35])[CH:14]=2)[CH:9]=1.C1COCC1.O>CCCCCC>[CH:27]1([NH:26][S:25]([C:22]2[CH:21]=[CH:20][C:19]([C:16]3[C:15]4[C:10](=[CH:11][CH:12]=[C:13]([F:35])[CH:14]=4)[CH:9]=[C:8]([CH2:7][C:6]([OH:36])=[O:5])[C:17]=3[CH3:18])=[CH:24][CH:23]=2)(=[O:34])=[O:33])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1

参加物

5

反応物 3

HCID 168937Lithium hydroxide, monohydrateHCID 21881883Oxolane--water (1/1)HCID 86695021[4-(4-Cyclohexylsulfamoyl-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester

生成物 1

HCID 71711512[4-(4-Cyclohexylsulfamoyl-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid収率 92.2%

試薬・触媒・溶媒 1

HCID 8058Hexane溶媒

実験手順

Lithium hydroxide monohydrate (0.018 g, 0.42 mmol) was added to a solution of [4-(4-cyclohexylsulfamoyl-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (0.05 g, 0.10 mmol) in a 3:1 mixture of THF—H2O mixture (6 mL). The reaction mixture was stirred for 16 hours at room temperature. The reaction mixture was concentrated to remove the THF, and the crude material was diluted with water, acidified [pH˜2] with a 6 N aqueous solution of hydrochloric acid. The mixture was extracted twice with ethyl acetate. The collected organic layers were washed with water and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to give the crude product. Trituration with hexane gave [4-(4-cyclohexylsulfamoyl-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid (0.042 g, 87%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.46 (br. s, 1 H), 7.95-8.06 (m, 3 H), 7.90 (s, 1 H), 7.72 (d, J=7.80 Hz, 1 H), 7.46 (d, J=8.31 Hz, 2 H), 7.38 (td, J=8.40, 2.40 Hz, 1 H), 6.63 (dd, J=11.20, 2.40 Hz, 1 H), 3.85 (s, 2 H), 3.00-3.09 (m, 1 H), 2.08 (s, 3 H), 1.52-1.67 (m, 4 H), 1.41-1.51 (m, 1H), 1.03-1.25 (m, 5H). MS calcd. for C25H25FNO4S [(M−H)−] 454, obsd. 454.4.

後処理

  1. concentrationThe reaction mixture was concentrated
  2. customto remove the THF
  3. additionthe crude material was diluted with water
  4. extractionThe mixture was extracted twice with ethyl acetate
  5. washThe collected organic layers were washed with water and brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude product

出典と根拠

ORDレコード
ord-9e61e3f568264ecb89d782021d5c5117
出典データセット
uspto-grants-2015_04
特許番号
US09000044B2

反応ノート

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