Sodium Hydroxide → 2-(4-{8-[(Cyclopropyl-methyl-amino)-methyl]-2,2,4,4-tetramethyl-chroman-6-ylethynyl}-phenyl)-2-methyl-propionic acid

HRID 1869849Notes

Reaction equation

HRID 1869849 reaction equation
C[O:2][C:3](=[O:35])[C:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][C:15]2[CH:16]=[C:17]3[C:22](=[C:23]([CH2:25][N:26]([CH:28]4[CH2:30][CH2:29]4)[CH3:27])[CH:24]=2)[O:21][C:20]([CH3:32])([CH3:31])[CH2:19][C:18]3([CH3:34])[CH3:33])=[CH:9][CH:8]=1)([CH3:6])[CH3:5].[OH-].[Na+]>CO.O1CCCC1>[CH:28]1([N:26]([CH2:25][C:23]2[CH:24]=[C:15]([C:14]#[C:13][C:10]3[CH:11]=[CH:12][C:7]([C:4]([CH3:6])([CH3:5])[C:3]([OH:35])=[O:2])=[CH:8][CH:9]=3)[CH:16]=[C:17]3[C:22]=2[O:21][C:20]([CH3:32])([CH3:31])[CH2:19][C:18]3([CH3:33])[CH3:34])[CH3:27])[CH2:30][CH2:29]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 690741872-(4-{8-[(Cyclopropyl-methyl-amino)-methyl]-2,2,4,4-tetramethyl-chroman-6-ylethynyl}-phenyl)-2-methyl-propionic acid methyl ester2×

Product 1

HCID 112133162-(4-{8-[(Cyclopropyl-methyl-amino)-methyl]-2,2,4,4-tetramethyl-chroman-6-ylethynyl}-phenyl)-2-methyl-propionic acidYield 27%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(4-{8-[(cyclopropyl-methyl-amino)-methyl]-2,2,4,4-tetramethyl-chroman-6-ylethynyl}-phenyl)-2-methyl-propionic acid methyl ester (Intermediate 15, 0.040 g, 0.084 mmol) in methanol (2.5 mL) and tetrahydrofuran (2.5 mL) was treated with a 2M solution of sodium hydroxide (1 mL, 2 mmol) and the resulting reaction mixture was refluxed overnight. The volatiles were evaporated in vacuo to a residue that was neutralized with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was washed with water and brine, and dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to an oil. Preparative reverse phase HPLC on a partisil 10 ODS-3 column using 10% water in acetonitrile as the mobile phase afforded the title compound (0.008 g, 27%).

Workup

  1. customthe resulting reaction mixture
  2. temperaturewas refluxed overnight
  3. customThe volatiles were evaporated in vacuo to a residue that
  4. extractionextracted with ethyl acetate
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo to an oil

Sources & evidence

ORD record
ord-1b5c380048ca44beba5fcf7a3152f3f2
Source dataset
uspto-grants-2009_12
Patent number
US07638648B2

Reaction notes

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