Lithium hydroxide, monohydrate → (S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid

HRID 19062Notes

Reaction equation

HRID 19062 reaction equation
C[O:2][C:3](=[O:26])[C@@H:4]([N:9]1[CH2:13][C:12]([O:14][C:15]2[C:24]3[CH2:23][CH2:22][CH2:21][CH2:20][C:19]=3[CH:18]=[CH:17][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[C:24]3[CH2:23][CH2:22][CH2:21][CH2:20][C:19]=3[CH:18]=[CH:17][CH:16]=2)=[CH:11][C:10]1=[O:25])[C:3]([OH:26])=[O:2]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66893856(S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid methyl ester

Product 1

HCID 66894447(S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acidYield 68.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid methyl ester (94 mg, 0.26 mmol) in tetrahydrofuran (1.5 mL) and water (0.5 mL) was treated with lithium hydroxide monohydrate (14 mg, 0.33 mmol). The reaction was stirred at 25° C. for 3 h. At this time, the reaction was concentrated in vacuo. The residue was diluted with water (25 mL) and was extracted with diethyl ether (1×25 mL). The aqueous layer was then acidified with a 1N aqueous hydrochloric acid solution and then extracted with 10% methanol/dichloromethane (2×25 mL). The organics were then dried over magnesium sulfate, filtered, rinsed with dichloromethane and concentrated in vacuo to afford (S)-4-methyl-2-[2-oxo-4-(5,6,7,8-tetrahydro-naphthalen-1-yloxy)-2,5-dihydro-pyrrol-1-yl]-pentanoic acid (61 mg, 67%) as an orange solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 0.87 (d, J=6.3 Hz, 3H), 0.93 (d, J=6.3 Hz, 3H), 1.36-1.84 (m, 7H), 2.53-2.61 (m, 2H), 2.68-2.83 (m, 2H), 4.12 (d, J=17.8 Hz, 1H), 4.24 (d, J=17.8 Hz, 1H), 4.62 (dd, J=11.2, 4.2 Hz, 1H), 4.66 (s, 1H), 6.99-7.07 (m, 2H), 7.18 (t, J=7.8 Hz, 1H), 12.84 (br. s., 1H).

Workup

  1. concentrationAt this time, the reaction was concentrated in vacuo
  2. additionThe residue was diluted with water (25 mL)
  3. extractionwas extracted with diethyl ether (1×25 mL)
  4. extractionextracted with 10% methanol/dichloromethane (2×25 mL)
  5. dry with materialThe organics were then dried over magnesium sulfate
  6. filtrationfiltered
  7. washrinsed with dichloromethane
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1dc3d49f06d84845aba83b6437e50b0b
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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