Water → 4-(4-Carboxymethyl-phenylethynyl)-2-[(cyclopropyl-methyl-amino)-methyl]-benzoic acid isopropyl ester

HRID 2377445Notes

Reaction equation

HRID 2377445 reaction equation
[CH:1]([O:4][C:5](=[O:31])[C:6]1[CH:11]=[CH:10][C:9]([C:12]#[C:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][C:21]([O:23]C)=[O:22])=[CH:16][CH:15]=2)=[CH:8][C:7]=1[CH2:25][N:26]([CH:28]1[CH2:30][CH2:29]1)[CH3:27])([CH3:3])[CH3:2].O1CCCC1.O.O.[OH-].[Li+]>CO>[CH:1]([O:4][C:5](=[O:31])[C:6]1[CH:11]=[CH:10][C:9]([C:12]#[C:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][C:21]([OH:23])=[O:22])=[CH:16][CH:15]=2)=[CH:8][C:7]=1[CH2:25][N:26]([CH:28]1[CH2:30][CH2:29]1)[CH3:27])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 69076258HCID 69076258, compound2×

Product 1

HCID 588834594-(4-Carboxymethyl-phenylethynyl)-2-[(cyclopropyl-methyl-amino)-methyl]-benzoic acid isopropyl esterYield 72.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-[(cyclopropyl-methyl-amino)-methyl]-4-(4-methoxycarbonylmethyl-phenylethynyl)-benzoic acid isopropyl ester (Intermediate 123, 0.1 g, 0.23 mmol) in a mixture of methanol (2 mL), tetrahydrofuran (2 mL) and water (1 mL) was treated with lithium hydroxide monohydrate (0.042 g, 1 mmol) and the resulting reaction mixture was stirred at ambient temperature for 2 h. The volatiles were evaporated in vacuo, the residue was neutralized with saturated, aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic extract was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a solid. Preparative reverse phase HPLC using 10% water in acetonitrile as the mobile phase afforded the title product as a white solid (0.068 g, 72%). 1H NMR (300 MHz, CDCl3): δ 9.05 (br s, 1H), 7.73 (d, 1H, J=8.4 Hz), 7.66 (s, 1H), 7.44-7.37 (m, 3H), 7.23-7.21 (m, 2H), 5.20 (heptet, 1H, J=6.0 Hz), 4.21 (s, 2H), 3.52 (s, 2H), 2.36 (s, 3H), 1.94 (m, 1H), 1.36 (d, 6H, J=6.0 Hz), 0.55-0.43 (m, 4H).

Workup

  1. customthe resulting reaction mixture
  2. customThe volatiles were evaporated in vacuo
  3. extractionextracted with ethyl acetate
  4. extractionThe combined organic extract
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo to a solid

Sources & evidence

ORD record
ord-0f55c44230c84532a863cc4456e903c4
Source dataset
uspto-grants-2008_12
Patent number
US07468391B2

Reaction notes

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