Lithium hydroxide, monohydrate → (S)-4-methyl-2-[2-oxo-4-(3-trifluoromethyl-phenoxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid

HRID 19050Notes

Reaction equation

HRID 19050 reaction equation
C[O:2][C:3](=[O:26])[C@@H:4]([N:9]1[CH2:13][C:12]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)=[CH:11][C:10]1=[O:25])[CH2:5][CH:6]([CH3:8])[CH3:7].O.[OH-].[Li+]>O1CCCC1.O>[CH3:7][CH:6]([CH3:8])[CH2:5][C@H:4]([N:9]1[CH2:13][C:12]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:22])[F:23])[CH:16]=2)=[CH:11][C:10]1=[O:25])[C:3]([OH:26])=[O:2]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66894456(S)-4-methyl-2-[2-oxo-4-(3-trifluoromethyl-phenoxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid methyl ester

Product 1

HCID 66893850(S)-4-methyl-2-[2-oxo-4-(3-trifluoromethyl-phenoxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acidYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (S)-4-methyl-2-[2-oxo-4-(3-trifluoromethyl-phenoxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid methyl ester (0.86 g, 2.32 mmol) in tetrahydrofuran (15 mL) and water (5 mL) was treated with lithium hydroxide monohydrate (0.12 g, 2.85 mmol). The reaction was stirred at 25° C. for 3 h. At this time, the reaction was diluted with water (75 mL) and extracted with diethyl ether (1×75 mL). The aqueous layer was acidified with a 2N aqueous hydrochloric acid solution and then extracted with ethyl acetate (3×50 mL). The combined organics were dried over magnesium sulfate, filtered, rinsed with ethyl acetate and concentrated in vacuo to afford (S)-4-methyl-2-[2-oxo-4-(3-trifluoromethyl-phenoxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid (0.71 g, 86%) as a light orange solid: HR-ES-MS m/z calculated for C17H18NO4F3 [M+H]+ 358.1261, observed 358.1262. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.88 (d, J=6.5 Hz, 3H), 0.93 (d, J=6.5 Hz, 3H), 1.50 (m, 1H), 1.57-1.70 (m, 1H), 1.70-1.86 (m, 1H), 4.16 (d, J=17.9 Hz, 1H), 4.28 (d, J=17.9 Hz, 1H), 4.64 (dd, J=11.6, 4.2 Hz, 1H), 4.93 (s, 1H), 7.65-7.77 (m, 4H), 12.88 (br. s., 1H).

Workup

  1. extractionextracted with diethyl ether (1×75 mL)
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. washrinsed with ethyl acetate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a6ce2e51570d472eaed05f7a143dc157
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

Loading…