Acetic Acid → Methyl 3-(isopropyl-amino)-5-phenylthiophene-2-carboxylate

HRID 73168

Reaction equation

HRID 73168 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].CO[C:19]([CH3:21])=[CH2:20].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.CCOC(C)=O.O>[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:19]([CH3:21])[CH3:20])=[O:4]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 83002-MethoxypropeneHCID 516892Sodium BicarbonateHCID 700562Methyl 3-amino-5-phenylthiophene-2-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 11737447Methyl 3-(isopropyl-amino)-5-phenylthiophene-2-carboxylateYield 96.4%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 3-Amino-5-phenyl-thiophene-2-carboxylic acid methyl ester (1.82 g, 7.8 mmol) in 1,2-dichloroethane (40 mL) was added sequentially 2-methoxypropene (3.0 mL, 31.2 mmol), AcOH (1.8 mL, 31.2 mmol) and NaBH(OAc)3 (3.31 g, 15.6 mmol) and stirred for 2 hrs. It was then diluted with EtOAc and H2O. The aqueous solution was adjusted to pH=7 by adding NaHCO3. The aqueous phase was extracted with EtOAc, the combined extract was washed with brine and dried on MgSO4 and filtered. Purification on bond elute with hexane to 5% EtOAc-hexane furnished 3-Isopropylamino-5-phenyl-thiophene-2-carboxylic acid methyl ester (2.07 g, 96% yield). 1H NMR (CDCl3, 400 MHz): δ 7.62 (d, 2H), 7.40 (m, 3H), 6.91 (s, 1H), 3.84 (s, 3H), 3.71 (m, 1H), 1.35 (d, 6H).

Workup

  1. extractionThe aqueous phase was extracted with EtOAc
  2. extractionthe combined extract
  3. washwas washed with brine
  4. customdried on MgSO4
  5. filtrationfiltered
  6. customPurification on bond
  7. washelute with hexane to 5% EtOAc-hexane

Sources & evidence

ORD record
ord-7eca7fdfe5a54abb85fa03b7ac19f993
Source dataset
uspto-grants-2014_09
Patent number
US08829030B2

Linked notes

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