Sodium Hydroxide → 4-(6-(5-{3-Cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2-{[(1,1-dimethylethyl)oxy]carbonyl}-5-methyl-1,2,3,4-tetrahydro-1-isoquinolinyl)butanoic acid

HRID 2383321Notes

Reaction equation

HRID 2383321 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[C:19]([CH3:43])=[C:20]4[C:25](=[CH:26][CH:27]=3)[CH:24]([CH2:28][CH2:29][CH2:30][C:31]([O:33]CC)=[O:32])[N:23]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:22][CH2:21]4)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].[OH-].[Na+]>C(O)C>[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[C:19]([CH3:43])=[C:20]4[C:25](=[CH:26][CH:27]=3)[CH:24]([CH2:28][CH2:29][CH2:30][C:31]([OH:33])=[O:32])[N:23]([C:36]([O:38][C:39]([CH3:40])([CH3:42])[CH3:41])=[O:37])[CH2:22][CH2:21]4)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2]

Participants

4

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 595910951,1-Dimethylethyl 6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-[4-(ethyloxy)-4-oxobutyl]-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate

Product 1

HCID 595910904-(6-(5-{3-Cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2-{[(1,1-dimethylethyl)oxy]carbonyl}-5-methyl-1,2,3,4-tetrahydro-1-isoquinolinyl)butanoic acidYield 96.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1,1-dimethylethyl 6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-[4-(ethyloxy)-4-oxobutyl]-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 29; 111 mg, 0.189 mmol) in ethanol (5 ml) was added 2M aqueous sodium hydroxide (0.189 ml, 0.377 mmol) and the resulting mixture was stirred at room temperature for 3 h. More 2M aqueous sodium hydroxide (2 equivalents) was added, and stirring was continued at room temperature for a further 3 h. Most of the solvent was removed and the residue partitioned between ethyl acetate and water. The aqueous layer was acidified with 2N aqueous hydrochloric acid, the layers separated, and the aqueous layer further extracted with ethyl acetate. The combined organic layers were dried over MgSO4 and concentrated in vacuo to give the title compound (102 mg) as a white foam.

Workup

  1. stirringstirring
  2. waitwas continued at room temperature for a further 3 h
  3. customMost of the solvent was removed
  4. customthe residue partitioned between ethyl acetate and water
  5. customthe layers separated
  6. extractionthe aqueous layer further extracted with ethyl acetate
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-36ca5fff28fa42418334c77ed4623eac
Source dataset
uspto-grants-2012_09
Patent number
US08263620B2

Reaction notes

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