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

HRID 2194116Notes

Reaction equation

HRID 2194116 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-962a0ee40f604f169e6fcc68e8d97d16
Source dataset
uspto-grants-2012_12
Patent number
US08329904B2

Reaction notes

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