Sodium Iodide → 4-(4-Chlorophenyl)-1-[3-(5,1 1-dihydro-7-(1-cyclohexyloxycarbonyloxy)ethyloxycarbonyl[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidin-4-ol Dihydrochloride

HRID 917067Notes

Reaction equation

HRID 917067 reaction equation
[C:1]([C:4]1[C:9]2[CH2:10][C:11](=[CH:19][CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][C:25]([C:29]4[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=4)([OH:28])[CH2:24][CH2:23]3)[C:12]3[C:13]([O:18][C:8]=2[CH:7]=[CH:6][CH:5]=1)=[N:14][CH:15]=[CH:16][CH:17]=3)([OH:3])=[O:2].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].[C:44](=[O:56])([O:52][CH:53]([Cl:55])[CH3:54])[O:45][CH:46]1[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1>CN(C)C=O.C(OCC)(=O)C.O>[ClH:35].[ClH:55].[Cl:35][C:32]1[CH:31]=[CH:30][C:29]([C:25]2([OH:28])[CH2:26][CH2:27][N:22]([CH2:21][CH2:20][CH:19]=[C:11]3[C:12]4[C:13](=[N:14][CH:15]=[CH:16][CH:17]=4)[O:18][C:8]4[CH:7]=[CH:6][CH:5]=[C:4]([C:1]([O:3][CH2:54][CH2:53][O:52][C:44]([O:45][CH:46]5[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]5)=[O:56])=[O:2])[C:9]=4[CH2:10]3)[CH2:23][CH2:24]2)=[CH:34][CH:33]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 112295291-Chloroethyl Cyclohexyl CarbonateHCID 667586701-[3-(7-Carboxy-5,11-dihydro[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]-4-(4-chlorophenyl)piperidin-4-ol

Product 1

HCID 667578324-(4-Chlorophenyl)-1-[3-(5,1 1-dihydro-7-(1-cyclohexyloxycarbonyloxy)ethyloxycarbonyl[1]benzoxepino[2,3-b]pyridin-5-ylidene)propyl]piperidin-4-ol DihydrochlorideYield 116.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of product of example 118 (1.1 g) in dimethylformamide (15 ml) were added sodium iodide (0.17 g), potassium carbonate (0.38 g) and cyclohexyl 1-chloroethyl carbonate (J. Antibiotics, 1987, 40, 81.) (0.57 g) at room temperature. The mixture was stirred at 70° C. for 1 hour. Water and ethyl acetate were added to the reaction mixture, the organic layer was separated and washed with saturated aqueous sodium chloride, and dried with magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate:methanol=100:3). The obtained oil was dissolved with ethyl acetate, and 4 N hydrochloric acid ethyl acetate solution (0.8 ml) was added. The precipitation was filtered to give the titled compound (0.96 g).

Workup

  1. customthe organic layer was separated
  2. washwashed with saturated aqueous sodium chloride
  3. dry with materialdried with magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (ethyl acetate:methanol=100:3)
  6. dissolutionThe obtained oil was dissolved with ethyl acetate, and 4 N hydrochloric acid ethyl acetate solution (0.8 ml)
  7. additionwas added
  8. customThe precipitation
  9. filtrationwas filtered

Sources & evidence

ORD record
ord-3727fbe00b034df4aebb1d692e996e8a
Source dataset
uspto-grants-2007_09
Patent number
US07271176B2

Reaction notes

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