Lithium Hydroxide → 3-{4-[2-(2,2,2-Trifluoroethoxy)-3-tert-butyl-5-methylphenyl]benzo[b]thien-2-yl}but-2-enoic acid

HRID 1394615Notes

Reaction equation

HRID 1394615 reaction equation
C([O:3][C:4](=[O:34])[CH:5]=[C:6]([C:8]1[S:12][C:11]2[CH:13]=[CH:14][CH:15]=[C:16]([C:17]3[CH:22]=[C:21]([CH3:23])[CH:20]=[C:19]([C:24]([CH3:27])([CH3:26])[CH3:25])[C:18]=3[O:28][CH2:29][C:30]([F:33])([F:32])[F:31])[C:10]=2[CH:9]=1)[CH3:7])C.C1COCC1.[Li+].[OH-]>CO>[F:33][C:30]([F:31])([F:32])[CH2:29][O:28][C:18]1[C:19]([C:24]([CH3:26])([CH3:25])[CH3:27])=[CH:20][C:21]([CH3:23])=[CH:22][C:17]=1[C:16]1[C:10]2[CH:9]=[C:8]([C:6]([CH3:7])=[CH:5][C:4]([OH:34])=[O:3])[S:12][C:11]=2[CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 692180713-{4-[2-(2,2,2-Trifluoroethoxy)-3-tert-butyl-5-methylphenyl]benzo[b]thien-2-yl}but-2-enoic acid ethyl ester

Product 1

HCID 668958623-{4-[2-(2,2,2-Trifluoroethoxy)-3-tert-butyl-5-methylphenyl]benzo[b]thien-2-yl}but-2-enoic acidYield 58%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 198 mg (0.41 mmol) of 3-{4-[2-(2,2,2-trifluoroethoxy)-3-tert-butyl-5-methylphenyl]benzo[b]thien-2-yl}but-2-enoic acid ethyl ester disolved in 4 mL of methanol, 5 mL of THF and 1 mL of a 2N aqueous solution of LiOH was heated to reflux for 2 hours. After cooling at room temperature and acidic work-up, the crude acid was purified using preparative HPLC (kromosil column, eluent: 8/92 water/methanol+0.1% TFA). Collection of the desired fractions, evaporation of the solvents and recrystallization from acetonitrile affords 110 mg (0.23 mmol, yield: 58%) of 3-{4-[2-(2,2,2-trifluoroethoxy)-3-tert-butyl-5-methylphenyl]benzo[b]thien-2-yl}but-2-enoic acid as a white solid. 1H NMR (400 MHz, CDCl3) d: 7.80 (d, J=8.2 Hz, 1H), 7.43 (t, J=7.7 Hz, 1H), 7.40 (s, 1H), 7.38 (d, J=8.2 Hz, 1H), 7.24 (d, J=1.9 Hz, 1H), 7.06 (d, J=1.9 Hz, 1H), 6.32 (s, 1H), 3.61 (m, 1H), 3.58 (m, 1H), 2.58 (s, 3H), 2.37 (s, 3H), 1.46 (s, 9H).

Workup

  1. temperatureto reflux for 2 hours
  2. customacidic work-up, the crude acid was purified
  3. customCollection of the desired
  4. customfractions, evaporation of the solvents and recrystallization from acetonitrile

Sources & evidence

ORD record
ord-4ddddb04d13943748c30c3e311a99f1e
Source dataset
uspto-grants-2008_03
Patent number
US07348359B2

Reaction notes

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