4-Cyanobenzoic acid → 4-{[(4-Cyano-benzoyl)-methyl-amino]-methyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 717066Notes

Reaction equation

HRID 717066 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1)#[N:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[C:43]([O:47][C:48]([N:50]1[CH2:55][CH2:54][CH:53]([CH2:56][NH:57][CH3:58])[CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:45])[CH3:44]>C(Cl)Cl.CN(C=O)C>[C:43]([O:47][C:48]([N:50]1[CH2:55][CH2:54][CH:53]([CH2:56][N:57]([C:7](=[O:9])[C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:11][CH:10]=2)[CH3:58])[CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:45])[CH3:44]

Participants

7

Reactant 4

HCID 120874-Cyanobenzoic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 21934652tert-Butyl 4-((methylamino)methyl)piperidine-1-carboxylate

Product 1

HCID 1179927504-{[(4-Cyano-benzoyl)-methyl-amino]-methyl}-piperidine-1-carboxylic acid tert-butyl esterYield 89.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-cyanobenzoic acid (322 mg, 2.19 mmol) in CH2Cl2 (10 mL) was added TBTU (702 mg, 2.19 mmol) and N,N-diisopropylethylamine (1.14 mL, 6.54 mmol) and the reaction mixture stirred at RT for 10 min. 4-Methylaminomethyl-piperidine-1-carboxylic acid tert-butyl ester (500 mg, 2.19 mmol) in DMF (4 mL) was added and the reaction mixture was stirred at RT for 2 h. The crude material was concentrated in vacuo and purified by silica gel column chromatography, eluting with isohexane and increasing the polarity to 100% EtOAc to afford 4-{[(4-cyano-benzoyl)-methyl-amino]-methyl}-piperidine-1-carboxylic acid tert-butyl ester as a orange solid (700 mg, 89%).

Workup

  1. stirringthe reaction mixture was stirred at RT for 2 h
  2. concentrationThe crude material was concentrated in vacuo
  3. custompurified by silica gel column chromatography
  4. washeluting with isohexane
  5. temperatureincreasing the polarity to 100% EtOAc

Sources & evidence

ORD record
ord-ff7899156f6446488c1ce83727c5ae3f
Source dataset
uspto-grants-2015_11
Patent number
US09193689B2

Reaction notes

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