Formaldehyde → (R)-1-(4-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-butyn-1-yl)-3-piperidinecarboxylic acid ethyl ester

HRID 413676

Reaction equation

HRID 413676 reaction equation
[CH2:1]([N:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[CH2:8][CH2:7][C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]1=2)[C:2]#[CH:3].[CH2:19]([O:21][C:22]([C@@H:24]1[CH2:29][CH2:28][CH2:27][NH:26][CH2:25]1)=[O:23])[CH3:20].[CH2:30]=O>O1CCOCC1>[CH2:19]([O:21][C:22]([C@@H:24]1[CH2:29][CH2:28][CH2:27][N:26]([CH2:30][C:3]#[C:2][CH2:1][N:4]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[CH2:8][CH2:7][C:6]3[CH:15]=[CH:16][CH:17]=[CH:18][C:5]2=3)[CH2:25]1)=[O:23])[CH3:20]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 185582ethyl (3R)-piperidine-3-carboxylateHCID 185214995-propargyl-10,11-dihydro-5H-dibenzo[b,f]azepine

Product 1

HCID 53904801(R)-1-(4-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-butyn-1-yl)-3-piperidinecarboxylic acid ethyl esterYield 83%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution containing 5-propargyl-10,11-dihydro-5H-dibenzo[b,f]azepine (2.45 g, 10.5 mmol, prepared similarly as described in U.S. Pat. No. 3,354,178 (1967)), (R)-3-piperidinecarboxylic acid ethyl ester (1.7 g, 10.8 mmol), paraformaldehyde (0.65 g) and a trace of cuprous chloride in dioxane (25 ml) was heated at reflux temperature for 5 h and left standing overnight. The mixture was filtered and the solvent evaporated. The remaining oil was purified by column chromatography on silica gel (40 g) using chloroform as eluent, affording 3.5 g (83%) of (R)-1-(4-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-butyn-1-yl)-3-piperidinecarboxylic acid ethyl ester.

Workup

  1. customprepared similarly
  2. temperatureat reflux temperature for 5 h
  3. waitleft
  4. filtrationThe mixture was filtered
  5. customthe solvent evaporated
  6. customThe remaining oil was purified by column chromatography on silica gel (40 g)

Sources & evidence

ORD record
ord-af394a8d7156425594b34b9f8356597f
Source dataset
uspto-grants-2003_05
Patent number
US06569849B1

Linked notes

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