Formaldehyde → HCID 178499314, compound

HRID 1808014Notes

Reaction equation

HRID 1808014 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][CH:7]=[CH:8][C:9]=1[N:10]([C:17]([C@H:19]1[CH2:24][CH2:23][C@H:22]([CH3:25])[CH2:21][CH2:20]1)=[O:18])[CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)=[O:4].[CH2:26]=O>ClCCCl>[CH3:1][O:2][C:3]([C:5]1[S:6][CH:7]=[CH:8][C:9]=1[N:10]([C:17]([C@H:19]1[CH2:20][CH2:21][C@H:22]([CH3:25])[CH2:23][CH2:24]1)=[O:18])[CH:11]1[CH2:12][CH2:13][N:14]([CH3:26])[CH2:15][CH2:16]1)=[O:4]

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 178499313HCID 178499313, compound

Product 1

HCID 178499314HCID 178499314, compoundYield 85.7%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirred solution of 3-[(trans-4-methyl-cyclohexanecarbonyl)-piperidin-4-yl-amino]-thiophene-2-carboxylic acid methyl ester (1.0 g, 2.7 mmol), from step 3, in 1,2-dichloroethane (10 mL) was sequentially added aq. 37% HCHO solution (0.45 mL, 5.4 mmol) and NaBH(OAC)3 (2.86 g, 13.5 mmol) in one portion, stirred for over night, reaction was then quenched with aq. 10% NaOH solution, extracted with DCM. The combined organic extract was washed with brine, dried, and concentrated to obtain 3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester (0.876 g, 85.5%) as a white solid. NMR 1H (CDCl3, 400 MHz): 7.54 (d, 1H), 6.86 (d, 1H), 4.7-4.6 (m, 1H), 3.85 (s, 3H), 2.9-2.7 (m, 2H), 2.22 (s, 3H), 2.15-1.1 (m, 14H), 0.8 (d, 3H), 0.75-0.5 (m, 2H).

Workup

  1. customwas then quenched with aq. 10% NaOH solution
  2. extractionextracted with DCM
  3. extractionThe combined organic extract
  4. washwas washed with brine
  5. customdried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-d9333ed87b8245969e8d9b59e65c20c7
Source dataset
uspto-grants-2013_01
Patent number
US08357718B2

Reaction notes

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