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Triethylamine → 4-(5-Bromo-2-hydroxy-phenylethynyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 533109
Notes
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Reaction equation

HRID 533109 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[CH:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[C:19](I)[CH:18]=1.C(N(CC)CC)C>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][C:21]2[CH:22]=[C:17]([Br:16])[CH:18]=[CH:19][C:20]=2[OH:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 109245324-Bromo-2-iodophenolHCID 15550481tert-Butyl 4-ethynylpiperidine-1-carboxylate

Product 1

HCID 866868774-(5-Bromo-2-hydroxy-phenylethynyl)-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalyst
HCID 178418476
HCID 178418476, compound
Catalyst
HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 4-ethynyl-piperidine-1-carboxylic acid tert-butyl ester (4.03 g), 4-bromo-2-iodo-phenol (5.00 g), Pd(PPh3)2Cl2 (600 mg), copper iodide (500 mg), and triethylamine (2.35 mL) in N,N-dimethylformamide (30 mL) is heated under an argon atmosphere to 75° C. for 4 h. The reaction mixture is diluted with ice water after cooling to room temperature and extracted with ethyl acetate. The combined extracts are dried over MgSO4 and concentrated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 80:20→60:40) to give the title compound. LC (method 2): tR=1.32 min; Mass spectrum (ESI+): m/z=402, 404 [M+Na]+.

Workup

  1. temperatureafter cooling to room temperature
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined extracts are dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 80:20→60:40)

Sources & evidence

ORD record
ord-3bf071de59db47d78f17ad6fcb8d0af7
Source dataset
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08853239B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes