Cesium carbonate → tert-butyl 4-{3-[(3R)-3-({1-[4-(2-fluoroethoxy)phenyl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

HRID 526318Notes

Reaction equation

HRID 526318 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24](=[O:39])[NH:25][CH:26]([C:32]3[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=3)[CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:47][CH2:48][F:49]>O1CCCC1>[F:49][CH2:48][CH2:47][O:38][C:35]1[CH:36]=[CH:37][C:32]([CH:26]([NH:25][C:24]([C@@H:20]2[CH2:21][CH2:22][CH2:23][N:18]([C:16](=[O:17])[CH2:15][CH2:14][CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12]3)[CH2:19]2)=[O:39])[CH2:27][C:28]([O:30][CH3:31])=[O:29])=[CH:33][CH:34]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 69804Ethane, 1-fluoro-2-iodo-HCID 712590204-(3-{(R)-3-[1-(4-hydroxy-phenyl)-2-methoxycarbonyl-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 89407580tert-butyl 4-{3-[(3R)-3-({1-[4-(2-fluoroethoxy)phenyl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylateYield 54.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

150 mg (0.28 mmol) 4-(3-{(R)-3-[1-(4-hydroxy-phenyl)-2-methoxycarbonyl-ethylcarbamoyl]-piperidin-1-yl}-3-oxo-propyl)-piperidine-1-carboxylic acid tert-butyl ester were dissolved in 3 ml tetrahydrofurane. 179 mg (0.55 mmol) cesium carbonate and 91 mg (0.52 mmol) 1-iodo-2-fluoroethane were added. The mixture was stirred at room temperature for 60 hours and filtrated. The filtrate was concentrated. Chromatography over 10 g silica gel (dichloromethane ethanol 100/0-90/10) gave 90 mg (50%) tert-butyl 4-{3-[(3R)-3-({1-[4-(2-fluoroethoxy)phenyl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate and 40 mg starting material.

Workup

  1. filtrationfiltrated
  2. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-b8b31cb88bea477dab8e7e95eef33ede
Source dataset
uspto-grants-2016_05
Patent number
US09345793B2

Reaction notes

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