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

HRID 1869927Notes

Reaction equation

HRID 1869927 reaction equation
C[O:2][C:3](=[O:34])/[C:4](/[CH3:33])=[CH:5]/[CH:6]1[CH2:11][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.C(OC(=O)/C(/C)=C/C1CC=C(C#CC2C=C(OC)C3C(N(C4CC4)C)CCC(C)(C)C=3C=2)C=C1)C.[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][CH:6](/[CH:5]=[C:4](\[CH3:33])/[C:3]([OH:34])=[O:2])[CH2:11][CH:10]=4)[CH:23]=[C:22]([O:24][CH3:25])[C:21]2=3)[CH2:30][CH2:29]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 86600190(E)-3-{4-[5-(cyclopropyl-methyl-amino)-4-methoxy-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ylethynyl]-cyclohexa-2,4-dienyl}-2-methyl-acrylic acid methyl esterHCID 86600191(E)-3-{4-[5-(Cyclopropyl-methyl-amino)-4-methoxy-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ylethynyl]-cyclohexa-2,4-dienyl}-2-methyl-acrylic acid ethyl ester

Product 1

HCID 21107273(E)-3-{4-[5-(Cyclopropyl-methyl-amino)-4-methoxy-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalen-2-ylethynyl]-cyclohexa-2,4-dienyl}-2-methyl-acrylic acidYield 49.4%

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]-cyclohexa-2,4-dienyl}-2-methyl-acrylic acid methyl ester (Intermediate 87, 0.12 g, 0.25 mmol) in methanol (3 mL) and tetrahydrofuran (2 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 recrystallized from hot acetonitrile to afford the title product as a white solid (0.055 g, 49%).

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
  7. customwas recrystallized from hot acetonitrile

Sources & evidence

ORD record
ord-bd71b1050ec248bd94268cb93f713f55
Source dataset
uspto-grants-2009_12
Patent number
US07638648B2

Reaction notes

Loading…