Hydrochloric Acid → (E)-3-{4-[5-(Cyclopropyl-methyl-amino)-4-methoxy-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ylethynyl]-phenyl}-acrylic acid

HRID 2377405Notes

Reaction equation

HRID 2377405 reaction equation
C[O:2][C:3](=[O:33])/[CH:4]=[CH:5]/[C:6]1[CH:11]=[CH:10][C:9]([C:12]#[C:13][C:14]2[CH:23]=[C:22]([O:24][CH3:25])[C:21]3[CH:20]([N:26]([CH:28]4[CH2:30][CH2:29]4)[CH3:27])[CH2:19][CH2:18][C:17]([CH3:32])([CH3:31])[C:16]=3[CH:15]=2)=[CH:8][CH:7]=1.[OH-].[K+].Cl>CO.O1CCCC1>[CH:28]1([N:26]([CH3:27])[CH:20]2[CH2:19][CH2:18][C:17]([CH3:32])([CH3:31])[C:16]3[CH:15]=[C:14]([C:13]#[C:12][C:9]4[CH:8]=[CH:7][C:6](/[CH:5]=[CH:4]/[C:3]([OH:33])=[O:2])=[CH:11][CH:10]=4)[CH:23]=[C:22]([O:24][CH3:25])[C:21]2=3)[CH2:29][CH2:30]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 57462493(E)-3-{4-[5-(Cyclopropyl-methyl-amino)-4-methoxy-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ylethynyl]-phenyl}-acrylic acid methyl ester2×

Product 1

HCID 21107274(E)-3-{4-[5-(Cyclopropyl-methyl-amino)-4-methoxy-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ylethynyl]-phenyl}-acrylic acidYield 35.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (E)-3-{4-[5-(cyclopropyl-methyl-amino)-4-methoxy-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ylethynyl]-phenyl}-acrylic acid methyl ester (Intermediate 86, 0.12 g, 0.27 mmol) in methanol (4 mL) and tetrahydrofuran (3 mL) was treated with a 3M solution of potassium hydroxide (1 mL, 3 mmol) and the resulting reaction mixture was stirred at ambient temperature overnight. 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 magnesium 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 white solid (0.041 g, 35%).

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 magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo to a residue that

Sources & evidence

ORD record
ord-1e3bd353ca5a4536b1a25362b908c9d7
Source dataset
uspto-grants-2008_12
Patent number
US07468391B2

Reaction notes

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