Acetic Acid → 3-(1-Methyl-piperidin-4-ylamino)-5-phenyl-thiophene-2-carboxylic acid methyl ester

HRID 73195

Reaction equation

HRID 73195 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].[CH3:17][N:18]1[CH2:23][CH:22]=[C:21](O[Si](C)(C)C)[CH2:20][CH2:19]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>ClC(Cl)C>[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][CH:21]1[CH2:22][CH2:23][N:18]([CH3:17])[CH2:19][CH2:20]1)=[O:4]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 700562Methyl 3-amino-5-phenylthiophene-2-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 100811201-Methyl-4-trimethylsilanyloxy-1,2,3,6-tetrahydro-pyridine

Product 1

HCID 207757493-(1-Methyl-piperidin-4-ylamino)-5-phenyl-thiophene-2-carboxylic acid methyl esterYield 73%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a stirred solution of methyl-3-amino-5-phenylthiophene-carboxylate (233 mg, 1.0 mmol) and 1-methyl-4-trimethylsilanyloxy-1,2,3,6-tetrahydro-pyridine (370 mg, 2.0 mmol) in dichloroethane (3.0 mL) was added AcOH (0.114 mL, 2.0 eq) and followed addition of NaBH(OAc)3 (424 mg, 2.0 mmol) in one portion. The resultant reaction mixture was stirred at RT for weekend, aq. 10% NaOH (until basic) was added, after 30 min, reaction mixture was extracted with dichloromethane. The organic extract was washed with brine and dried. The crude product was purified on silica gel column using 20% EtOAc/hexane for unreacted starting material followed by CHCl3/MeOH/Et3N (180/16/1) furnished the 3-(1-methyl-piperidin-4-ylamino)-5-phenyl-thiophene-2-carboxylic acid methyl ester (240 mg, 73%). NMR 1H (CDCl3, 400 MHz): 7.64-7.6 (m, 2H), 7.43-7.34 (m, 3H), 6.83 (brs, 2H), 3.83 (s, 3H), 3.46-3.4 (m, 1H), 2.82-2.74 (m, 1H), 2.3 (s, 3H), 2.26-2.2 (m, 4H), 1.72-1.62 (m, 2H).

Workup

  1. customThe resultant reaction mixture
  2. customreaction mixture
  3. extractionwas extracted with dichloromethane
  4. extractionThe organic extract
  5. washwas washed with brine
  6. customdried
  7. customThe crude product was purified on silica gel column

Sources & evidence

ORD record
ord-5108744bbdbd495fb6d10a4012885767
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Linked notes

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