Acetic Acid → 5-(4-Fluoro-phenyl)-3-isopropylamino-thiophene-2-carboxylic acid methyl ester

HRID 749375

Reaction equation

HRID 749375 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[CH:8][C:9]=1[NH2:10])=[O:4].CO[C:20]([CH3:22])=[CH2:21].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][C:14]([F:17])=[CH:13][CH:12]=2)=[CH:8][C:9]=1[NH:10][CH:20]([CH3:22])[CH3:21])=[O:4]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 83002-MethoxypropeneHCID 516892Sodium BicarbonateHCID 619692Methyl 3-amino-5-(4-fluorophenyl)thiophene-2-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 597523015-(4-Fluoro-phenyl)-3-isopropylamino-thiophene-2-carboxylic acid methyl esterYield 92%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 3-amino-5-(4-fluoro-phenyl)-thiophene-2-carboxylic acid methyl ester (0.502 g, 2.0 mmol) in 1,2-dichloroethane (6.0 mL) was added sequentially 2-methoxypropene (0.38 mL, 4.0 mmol), AcOH (0.114 mL, 2.0 mmol) and NaBH(OAc)3 (0.84 g, 4.0 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 10% EtOAc-hexane furnished 5-(4-fluoro-phenyl)-3-isopropylamino thiophene-2-carboxylic acid methyl ester (0.538 g, 92% yield).

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 10% EtOAc-hexane

Sources & evidence

ORD record
ord-7f9a939f6e2249d795fb8f0cd67fb85c
Source dataset
uspto-grants-2008_07
Patent number
US07402608B2

Linked notes

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