Hydrochloric Acid → {8-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethylsulfanyl]-chroman-5-yloxy}-acetic acid

HRID 2307878Notes

Reaction equation

HRID 2307878 reaction equation
C[O:2][C:3](=[O:34])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([S:16][CH2:17][C:18]2[S:22][C:21]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[N:20][C:19]=2[CH3:33])=[C:12]2[C:7]=1[CH2:8][CH2:9][CH2:10][O:11]2.O.[OH-].[Li+].Cl>C1COCC1.O>[CH3:33][C:19]1[N:20]=[C:21]([C:23]2[CH:24]=[CH:25][C:26]([C:29]([F:32])([F:30])[F:31])=[CH:27][CH:28]=2)[S:22][C:18]=1[CH2:17][S:16][C:13]1[CH:14]=[CH:15][C:6]([O:5][CH2:4][C:3]([OH:34])=[O:2])=[C:7]2[C:12]=1[O:11][CH2:10][CH2:9][CH2:8]2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 11179744{8-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethylsulfanyl]-chroman-5-yloxy}-acetic acid methyl ester

Product 1

HCID 10195850{8-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethylsulfanyl]-chroman-5-yloxy}-acetic acidYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

{8-[4-Methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethylsulfanyl]-chroman-5-yloxy}-acetic acid methyl ester dissolved in 5 ml THF and 1 ml water, was treated with lithium hydroxide monohydrate (327 mg, 7.8 mmol); stirring at room temperature for 1 hour. The reaction mixture was then acidified to about pH 3 with 2 N HCl. The reaction was then extracted into ethyl acetate (2×20 ml). The organic extracts were washed with brine, dried over anhydrous sodium sulfate, decanted, and concentrated in vacuo. Recrystalization from chloroform/hexanes afforded the title compound (750 mg, 96%) as a pale yellow solid. IR (thin film) cm−1: 1745; 400 MHz 1H NMR (DMSO-d6) δ 7.98 (d, 2H, J=8.0 Hz), 7.75 (d, 2H, J=8.0 Hz), 6.97 (d, 1H, J=8.5 Hz), 6.27 (d, 1H, J=8.5 Hz), 4.60 (s, 2H), 4.18 (s, 2H), 4.11 (t, 2H, J=4.6 Hz), 2.56 (t, 2H, J=6.6 Hz), 2.15 (s, 3H), 1.83 (m, 2H).; MS m/z 496 (M+1). Anal. Calc'd for C23H20F3N1O4S2 0.3 CHCl3 C, 52.67; H, 3.85; N, 2.64; found: C, 52.49; H, 3.77; N, 2.54.

Workup

  1. extractionThe reaction was then extracted into ethyl acetate (2×20 ml)
  2. washThe organic extracts were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customdecanted
  5. concentrationconcentrated in vacuo
  6. customRecrystalization from chloroform/hexanes

Sources & evidence

ORD record
ord-abff5dc83e574479a48a2b14224783b8
Source dataset
uspto-grants-2004_12
Patent number
US06833380B2

Reaction notes

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