4-Methylmorpholine → (4-{[1-(2-Chloro-benzenesulfonyl)-4-(2-methoxy-ethyl)-piperidine-4-carbonyl]-amino}-phenyl)-acetic acid ethyl ester

HRID 2194116ノート

反応式

HRID 2194116 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([N:11]1[CH2:16][CH2:15][C:14]([CH2:20][CH2:21][O:22][CH3:23])([C:17](O)=[O:18])[CH2:13][CH2:12]1)(=[O:10])=[O:9].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[CH2:48]([O:50][C:51](=[O:60])[CH2:52][C:53]1[CH:58]=[CH:57][C:56]([NH2:59])=[CH:55][CH:54]=1)[CH3:49].CN1CCOCC1>C1COCC1>[CH2:48]([O:50][C:51](=[O:60])[CH2:52][C:53]1[CH:54]=[CH:55][C:56]([NH:59][C:17]([C:14]2([CH2:20][CH2:21][O:22][CH3:23])[CH2:13][CH2:12][N:11]([S:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])(=[O:9])=[O:10])[CH2:16][CH2:15]2)=[O:18])=[CH:57][CH:58]=1)[CH3:49]

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 225219p-Aminophenylacetic acid ethyl esterHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 595780921-(2-Chloro-benzenesulfonyl)-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid

生成物 1

HCID 59578103(4-{[1-(2-Chloro-benzenesulfonyl)-4-(2-methoxy-ethyl)-piperidine-4-carbonyl]-amino}-phenyl)-acetic acid ethyl ester収率 60.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

1-(2-Chloro-benzenesulfonyl)-4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid (2.82 g) were dissolved in THF (30 ml) under an argon atmosphere at RT and then sequentially treated with O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) (3.26 g), (4-amino-phenyl)-acetic acid ethyl ester (1.536 g) and N-methyl morpholine (1.04 ml). The reaction mixture was stirred 12 h at RT, and 1 h at reflux to complete the reaction. The mixture was partitioned between AcOEt and 1N HCl/water, the layers were separated; the organic layer was dried over sodium sulphate and then removed in vacuo. The residue was purified by chromatography on silica gel (CH2Cl2/AcOEt, 19/1 to 9/1) to give the desired (4-{[1-(2-chloro-benzenesulfonyl)-4-(2-methoxy-ethyl)-piperidine-4-carbonyl]-amino}-phenyl)-acetic acid ethyl ester (2.47 g) which was directly used in the next step.

後処理

  1. temperature1 h at reflux
  2. customthe reaction
  3. customThe mixture was partitioned between AcOEt and 1N HCl/water
  4. customthe layers were separated
  5. dry with materialthe organic layer was dried over sodium sulphate
  6. customremoved in vacuo
  7. customThe residue was purified by chromatography on silica gel (CH2Cl2/AcOEt, 19/1 to 9/1)

出典と根拠

ORDレコード
ord-962a0ee40f604f169e6fcc68e8d97d16
出典データセット
uspto-grants-2012_12
特許番号
US08329904B2

反応ノート

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