Lithium hydroxide, monohydrate → 2-(Tert-butoxycarbonyl)-1-butyl-1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid

HRID 14269Notes

Reaction equation

HRID 14269 reaction equation
[CH2:1]([CH:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([O:17]C)=[O:16])[CH:13]=2)[CH2:8][CH2:7][N:6]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:2][CH2:3][CH3:4].O.[OH-].[Li+]>O1CCOCC1.CO.O>[C:22]([O:21][C:19]([N:6]1[CH2:7][CH2:8][C:9]2[C:14](=[CH:13][C:12]([C:15]([OH:17])=[O:16])=[CH:11][CH:10]=2)[CH:5]1[CH2:1][CH2:2][CH2:3][CH3:4])=[O:20])([CH3:25])([CH3:24])[CH3:23]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 57487398HCID 57487398, compound

Product 1

HCID 210856402-(Tert-butoxycarbonyl)-1-butyl-1,2,3,4-tetrahydroisoquinoline-7-carboxylic acidYield 61.5%

Reagents, catalysts & solvents 1

HCID 22592949Dioxane methanol waterSolvent

Procedure

To a solution of 2-tert-butyl 7-methyl 1-butyl-3,4-dihydroisoquinoline-2,7(1H)-dicarboxylate prepared in step 2 (347 mg, 1.0 mmol) in 2:1:1 dioxane/methanol/water (6.6 mL) was added lithium hydroxide monohydrate (125 mg, 3.0 mmol) and the reaction mixture stirred 24 h at room temperature. The reaction mixture was concentrated under reduced pressure and the solid residue partitioned between ethyl acetate and water. The aqueous phase was acidified with 1 N hydrochloric acid to pH 1 and extracted several times with 3:1 chloroform/2-propanol. The combined organic phases were washed with water and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure to provide 2-(tert-butoxycarbonyl)-1-butyl-1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid (205 mg). ESI MS m/z 332 [M−H]−.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe solid residue partitioned between ethyl acetate and water
  3. extractionextracted several times with 3:1 chloroform/2-propanol
  4. washThe combined organic phases were washed with water and saturated sodium chloride
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-aadc9f8d41d94c9685479eaa05ae039d
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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