Ethanol → (S)-2-(5-(2-(2-(4-isopropylphenyl)-5-methylthiazol-4-yl)ethoxy)-2,3-dihydro-1H-inden-1-yl)acetic acid

HRID 900540Notes

Reaction equation

HRID 900540 reaction equation
C([O:3][C:4](=[O:25])[CH2:5][C@H:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH2:16][CH2:17][C:18]3[N:19]=[C:20](Br)[S:21][C:22]=3[CH3:23])=[CH:12][CH:13]=2)[CH2:8][CH2:7]1)C.[CH3:26][CH2:27]O.[Li+].[OH-]>C1COCC1.O>[CH:9]([C:26]1[CH:27]=[CH:7][C:6]([C:20]2[S:21][C:22]([CH3:23])=[C:18]([CH2:17][CH2:16][O:15][C:11]3[CH:10]=[C:9]4[C:14](=[CH:13][CH:12]=3)[C@H:6]([CH2:5][C:4]([OH:3])=[O:25])[CH2:7][CH2:8]4)[N:19]=2)=[CH:5][CH:4]=1)([CH3:10])[CH3:8]

Participants

6

Reactant 3

HCID 702EthanolHCID 3939Lithium HydroxideHCID 58700766ethyl{(1S)-5-[2-(2-bromo-5-methyl-1,3-thiazol-4-yl)ethoxy]-2,3-dihydro-1H-inden-1-yl}acetate

Product 1

HCID 10274664(S)-2-(5-(2-(2-(4-isopropylphenyl)-5-methylthiazol-4-yl)ethoxy)-2,3-dihydro-1H-inden-1-yl)acetic acidYield 66%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Example 174 (305 mg, 0.657 mmol) in a mixture of THF (8 mL), water (8 mL), and EtOH (4 mL), was added LiOH (63 mg, 2.63 mmol). The reaction mixture was vigorously stirred for 24 hours, diluted with water (20 mL), and washed with Et2O (10 mL). The aqueous phase was then acidified to pH ˜1 using 1 N HCl, and then extracted with CH2Cl2 (4×50 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was then purified by silica gel flash chromatography (95:5 CH2Cl2/MeOH) to afford product (189 mg, 66%) as a white solid. (C26H29NO3S): LC-MS, RT 3.95 min., M+H 436.4; 1H NMR (CDCl3): δ 1.25 (s, 3H), 1.28 (s, 3H), 1.70-1.82 (m, 1H), 2.32-2.43 (m, 2H), 2.45 (s, 3H), 2.74-2.98 (m, 4H), 3.18 (t, 2H), 3.47-3.54 (m, 1H), 4.28 (t, 2H), 6.72 (dd, 1H), 6.78 (s, 1H), 7.08 (d, 1H), 7.51 (AB quartet, 4H).

Workup

  1. washwashed with Et2O (10 mL)
  2. extractionextracted with CH2Cl2 (4×50 mL)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was then purified by silica gel flash chromatography (95:5 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-e1e5029dda894b95abcfb292fe01772e
Source dataset
uspto-grants-2008_04
Patent number
US07358386B2

Reaction notes

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