Trifluoroacetic acid → 6-(Carboxy-fluoro-methyl)-benzo[b]thiophene-2-carboxylic acid ethyl ester

HRID 1172896Notes

Reaction equation

HRID 1172896 reaction equation
C([O:5][C:6](=[O:30])[C:7]([C:16]1[CH:29]=[CH:28][C:19]2[CH:20]=[C:21]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[S:22][C:18]=2[CH:17]=1)([F:15])C(OC(C)(C)C)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:26]([O:25][C:23]([C:21]1[S:22][C:18]2[CH:17]=[C:16]([CH:7]([C:6]([OH:30])=[O:5])[F:15])[CH:29]=[CH:28][C:19]=2[CH:20]=1)=[O:24])[CH3:27]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59556415Di-tert-butyl [2-(ethoxycarbonyl)-1-benzothien-6-yl](fluoro)malonate

Product 1

HCID 595564126-(Carboxy-fluoro-methyl)-benzo[b]thiophene-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Di-tert-butyl[2-(ethoxycarbonyl)-1-benzothien-6-yl](fluoro)malonate (9.3 g) was stirred in DCM (40 mL)/TFA (20 mL) at room temperature overnight. The solvent was removed in vacuo and the residue partitioned between saturated NaHCO3-EtOAc. The aqueous phase was acidified with 2N HCl and extracted with EtOAc. The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was suspended in H2O (50 mL) and heated to reflux for 2 hours. Room temperature was attained and the products extracted into EtOAc. The combined organic extracts were dried over MgSO4 and concentrated in vacuo to give the product as a pale yellow solid. 1H NMR (DMSO-d6) δ 13.60 (br s, 1H), 8.22 (s, 1H), 8.18 (s, 1H), 8.08 (d, J=8.4 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 6.14 (d, J=47.4 Hz, 1H), 4.35 (q, J=7.2 Hz, 2H), 1.33 (t, J=7.2 Hz, 3H).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue partitioned between saturated NaHCO3-EtOAc
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. temperatureheated
  7. temperatureto reflux for 2 hours
  8. customRoom temperature
  9. extractionthe products extracted into EtOAc
  10. dry with materialThe combined organic extracts were dried over MgSO4
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-70629aa5ecde4879a97e4f9c01404ab5
Source dataset
uspto-grants-2010_11
Patent number
US07834034B2

Reaction notes

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