Water → Methanesulfonic acid 7,9-difluoro-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5H-6-thia-chrysen-2-yl ester

HRID 1513937ノート

反応式

HRID 1513937 の反応式
[F:1][C:2]1[C:3]([S:41]C)=[C:4]([C:9]2[C:10]([CH:24](O)[C:25]3[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][N:34]4[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]4)=[CH:27][CH:26]=3)=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[C:14]([O:19][S:20]([CH3:23])(=[O:22])=[O:21])[CH:13]=[CH:12]3)[CH:5]=[C:6]([F:8])[CH:7]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]2[C:3]=1[S:41][CH:24]([C:25]1[CH:26]=[CH:27][C:28]([O:31][CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)=[CH:29][CH:30]=1)[C:10]1[C:9]2=[CH:18][CH:17]=[C:16]2[C:11]=1[CH:12]=[CH:13][C:14]([O:19][S:20]([CH3:23])(=[O:21])=[O:22])=[CH:15]2

参加物

6

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86626530Methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-{hydroxy-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl}-naphthalen-2-yl ester

生成物 1

HCID 11273238Methanesulfonic acid 7,9-difluoro-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5H-6-thia-chrysen-2-yl ester収率 74.5%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Dissolve methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-{hydroxy-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl}-naphthalen-2-yl ester (7.4 g, 12 mmol) in dry methylene chloride (200 mL) and purge with nitrogen. Add triethylamine (8.3 mL, 60 mmol) followed by methanesulfonyl chloride (4.6 mL, 60 mmol). After 30 minutes, pour reaction into water and extract with methylene chloride. Wash organic layer with water, dry over sodium sulfate, filter and concentrate. Purify over silica gel, eluting with 0 to 3% methanol in methylene chloride, to yield 5.2 g (74%) of the title compound. LCMS Rt (0.01% heptafluorobutyric acid:1.0% isopropylalcohol:water is mobile phase A and 0.01% heptafluorobutyric acid:1.0% isopropylalcohol:acetonitrile is mobile phase B; gradient method 25 to 95% B, Purity@254 nm)=3.34 min (100%); mass spectrum (ion spray): m/z=582.2 (M+H).

後処理

  1. custompurge with nitrogen
  2. additionpour
  3. extractionextract with methylene chloride
  4. dry with materialWash organic layer with water, dry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify over silica gel
  8. washeluting with 0 to 3% methanol in methylene chloride

出典と根拠

ORDレコード
ord-12702aa45da542809866c81e3bc5c98e
出典データセット
uspto-grants-2012_07
特許番号
US08217032B2

反応ノート

読み込み中…