Phenylsilane → 3-[(1-Methyl-piperidin-3-ylmethyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester

HRID 749326

Reaction equation

HRID 749326 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:8][C:9]=1[NH2:10])=[O:4].[CH:17]([CH:19]1[CH2:24][CH2:23][CH2:22][N:21]([C:25](OCC2C=CC=CC=2)=O)[CH2:20]1)=O.C1([SiH3])C=CC=CC=1>C1COCC1.CCOC(C)=O.C([Sn](Cl)(Cl)CCCC)CCC>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:8][C:9]=1[NH:10][CH2:17][CH:19]1[CH2:24][CH2:23][CH2:22][N:21]([CH3:25])[CH2:20]1)=[O:4]

Participants

7

Reactant 3

HCID 12752PhenylsilaneHCID 700562Methyl 3-amino-5-phenylthiophene-2-carboxylateHCID 9899653Benzyl 3-formylpiperidine-1-carboxylate

Product 1

HCID 684258443-[(1-Methyl-piperidin-3-ylmethyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl esterYield 68.7%

Reagents, catalysts & solvents 3

HCID 12688Dibutyltin dichlorideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 3-amino-5-phenyl-thiophene-2-carboxylic acid methyl ester (0.268 g, 1.15 mmol) and 3-formyl N-Cbz-piperidine (0.284 g, 1.15 mmol) in THF (0.5 mL) was treated with dibutyltin dichloride (17 mg, 0.057 mmol). After 5 min, phenylsilane (156 □L, 1.26 mmol) was added and the mixture was stirred for 6 days at room temperature. The solvent was then evaporated and the residue was purified by silica gel column chromatography using CH2Cl2:hexanes:EtOAc as eluent to provide 3-[(1-Methyl-piperidin-3-ylmethyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester as an oil (0.2723 g, 51% yield). 1H NMR (CDCl3, 400 MHz): 7.63-7.59 (m, 2H), 7.40-7.28 (m, 9H), 7.18-6.84 (br s, 1H), 5.20 (d, 1H), 5.10 (d, 1H), 4.55 (m, 1H), 4.15 (m, 1H), 3.82 (s, 3H), 3.58-3.40 (m, 2H), 2.90 (t, 1H), 1.88-1.40 (m, 6H).

Workup

  1. customThe solvent was then evaporated
  2. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7172c53f31db42db849765f403df280a
Source dataset
uspto-grants-2008_07
Patent number
US07402608B2

Linked notes

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