Hydrochloric Acid → 2-{4-[5-(Cyclopropyl-methyl-amino)-4-methoxy-8,8-dimethyl-5,6,7,8-tetrahydronaphthalen-2-ylethynyl]-phenyl}-2-methyl-propionic acid

HRID 2377403Notes

Reaction equation

HRID 2377403 reaction equation
C[O:2][C:3](=[O:34])[C:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][C:15]2[CH:24]=[C:23]([O:25][CH3:26])[C:22]3[CH:21]([N:27]([CH:29]4[CH2:31][CH2:30]4)[CH3:28])[CH2:20][CH2:19][C:18]([CH3:33])([CH3:32])[C:17]=3[CH:16]=2)=[CH:9][CH:8]=1)([CH3:6])[CH3:5].[OH-].[K+].Cl>CO.O1CCCC1>[CH:29]1([N:27]([CH3:28])[CH:21]2[CH2:20][CH2:19][C:18]([CH3:32])([CH3:33])[C:17]3[CH:16]=[C:15]([C:14]#[C:13][C:10]4[CH:9]=[CH:8][C:7]([C:4]([CH3:5])([CH3:6])[C:3]([OH:34])=[O:2])=[CH:12][CH:11]=4)[CH:24]=[C:23]([O:25][CH3:26])[C:22]2=3)[CH2:30][CH2:31]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 574242462-{4-[5-(Cyclopropyl-methyl-amino)-4-methoxy-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ylethynyl]-phenyl}-2-methyl-propionic acid methyl ester2×

Product 1

HCID 211071282-{4-[5-(Cyclopropyl-methyl-amino)-4-methoxy-8,8-dimethyl-5,6,7,8-tetrahydronaphthalen-2-ylethynyl]-phenyl}-2-methyl-propionic acidYield 65.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-{4-[5-(cyclopropyl-methyl-amino)-4-methoxy-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ylethynyl]-phenyl}-2-methyl-propionic acid methyl ester (Intermediate 85, 0.09 g, 0.196 mmol) in methanol (3 mL) and tetrahydrofuran (2 mL) was treated with a 3M solution of potassium hydroxide (1.5 mL, 4.5 mmol) and the resulting reaction mixture was stirred at ambient temperature for 3 days. The reaction mixture was neutralized with 5% aqueous hydrochloric acid and extracted with ethyl acetate. The organic phase was washed with water and brine, and dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to a residue that was subjected to flash column chromatography over silica gel (230-400 mesh) using 5% methanol in ethyl acetate as the eluent to afford the title product as a yellow solid (0.057 g, 65%).

Workup

  1. customthe resulting reaction mixture
  2. extractionextracted with ethyl acetate
  3. washThe organic phase was washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo to a residue that

Sources & evidence

ORD record
ord-67f49563663a42e4a58521b89905a284
Source dataset
uspto-grants-2008_12
Patent number
US07468391B2

Reaction notes

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