Formaldehyde → HCID 59752297, compound

HRID 73155Notes

Reaction equation

HRID 73155 reaction equation
C(O[C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][N:18]([C:28]2[CH:32]=[C:31]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[S:30][C:29]=2[C:39]([O:41][CH3:42])=[O:40])[C:19]([CH:21]2[CH2:26][CH2:25][CH:24]([CH3:27])[CH2:23][CH2:22]2)=[O:20])[CH2:13][CH2:12]1)=O)C1C=CC=CC=1.C=O>CO.CC(O)=O.[Pd]>[CH3:42][O:41][C:39]([C:29]1[S:30][C:31]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[CH:32][C:28]=1[N:18]([C:19]([CH:21]1[CH2:26][CH2:25][CH:24]([CH3:27])[CH2:23][CH2:22]1)=[O:20])[CH2:17][CH:14]1[CH2:15][CH2:16][N:11]([CH3:9])[CH2:12][CH2:13]1)=[O:40]

Participants

6

Reactant 2

HCID 712FormaldehydeHCID 597523324-{[(2-Methoxycarbonyl-5-phenyl-thiophen-3-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-methyl}-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 59752297HCID 59752297, compoundYield 31%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Procedure

4-{[(2-Methoxycarbonyl-5-phenyl-thiophen-3-yl)-(4-methyl-cyclohexanecarbonyl)-amino]-methyl}-piperidine-1-carboxylic acid benzyl ester (190 mg, 0.32 mmol) was dissolved in MeOH (3.2 mL) and treated with formaldehyde (37% solution, 0.36 mL, 3.2 mmol), AcOH (1 drop) and 10% Pd/C (97 mg) under H2 (30 psi). The reaction was stirred at room temperature for 48 h and the mixture was filtered on celite. The solution was evaporated to a residue that was purified by silica gel column chromatography using CH2Cl2:MeOH as eluent to provide 3-[(4-Methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-ylmethyl)-amino]-5-phenyl-thiophene-2-carboxylic acid methyl ester as an oil (46.5 mg, 31% yield). 1H NMR (CDCl3, 400 MHz): 7.62 (d, 2H), 7.43 (m, 3H), 7.10 (s, 1H), 3.97 (m, 1H), 3.85 (s, 3H), 3.20 (m, 3H), 2.48 (s, 3H), 2.42 (m, 1H), 2.10 (m, 1H), 1.85 (m, 3H), 1.70-1.40 (m, 8H), 1.30 (m, 2H), 0.78 (d, 3H), 0.68 (m, 2H).

Workup

  1. filtrationthe mixture was filtered on celite
  2. customThe solution was evaporated to a residue that
  3. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f90dfdf06c814f42a316097a4a0f9380
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Reaction notes

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