Water → HCID 58883455, compound

HRID 1869967Notes

Reaction equation

HRID 1869967 reaction equation
[CH:1]([O:4][C:5](=[O:32])[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])=[C:16]([F:25])[CH:15]=2)=[CH:8][C:7]=1[CH2:26][N:27]([CH:29]1[CH2:31][CH2:30]1)[CH3:28])([CH3:3])[CH3:2].O1CCCC1.O.O.[OH-].[Li+]>CO>[CH:1]([O:4][C:5](=[O:32])[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])=[C:16]([F:25])[CH:15]=2)=[CH:8][C:7]=1[CH2:26][N:27]([CH:29]1[CH2:31][CH2:30]1)[CH3:28])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 690779862-[(Cyclopropyl-methyl-amino)-methyl]-4-(3-fluoro-4-methoxycarbonylmethyl-phenylethynyl)-benzoic acid isopropyl ester2×

Product 1

HCID 58883455HCID 58883455, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-[(cyclopropyl-methyl-amino)-methyl]-4-(3-fluoro-4-methoxycarbonylmethyl-phenylethynyl)-benzoic acid isopropyl ester (Intermediate 124, 0.04 g, 0.09 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 (0.026 g, 54%). 1H NMR (300 MHz, CDCl3): δ 7.71 (d, 1H, J=8.1 Hz), 7.64 (s, 1H), 7.41 (d, 1H, J=8.1 Hz), 7.17-7.09 (m, 3H), 5.20 (heptet, 1H, J=6.3 Hz), 4.16 (s, 2H), 3.54 (s, 2H), 2.34 (s, 3H), 1.91 (m, 1H), 1.36 (d, 6H, J=6.3 Hz), 0.50-0.41 (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-13458e745f954cb6b7f633da4550a0eb
Source dataset
uspto-grants-2009_12
Patent number
US07638648B2

Reaction notes

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