Ethyl Acetate → 2-Cyclopropyl-6-hydroxy-4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline
Reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([CH:12]=O)[CH2:6][C:5]2([CH3:15])[CH3:14].[CH2:16]([Mg]Br)[CH3:17].C(OCC)(=O)C>O1CCCC1.C(OCC)C.CCCCCC>[CH:12]1([N:7]2[CH2:6][C:5]([CH3:15])([CH3:14])[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([OH:1])[CH:3]=3)[CH2:8]2)[CH2:17][CH2:16]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 55 °C
Procedure
A stirred, cooled (0° C.)solution of 6-hydroxy-4,4-dimethyl-1,2,3,4-tetrahydro-isoquinoline-2-carbaldehyde (Intermediate 20, 2.3 g, 11.21 mmol) in anhydrous tetrahydrofuran (40 mL) under argon was treated with titanium tetra-iso-propoxide (8.28 mL, 28 mmol) followed by 3M solution of ethyl magnesium bromide in diethyl ether (18.7 mL) and the reaction mixture was then heated at 55° C. overnight. It was then cooled in an ice-bath, quenched with saturated aqueous ammonium chloride solution and extracted with diethyl ether (×2). The combined organic phase was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to afford a yellow oily solid. Flash column chromatography over silica gel (230-400 mesh) using 10-20% ethyl acetate in hexane as the eluent afforded the title compound as a pale yellow solid (1.55 g, 63%).
Workup
- temperatureIt was then cooled in an ice-bath
- customquenched with saturated aqueous ammonium chloride solution
- extractionextracted with diethyl ether (×2)
- dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
- filtrationfiltered
- customevaporated in vacuo
- customto afford a yellow oily solid
Sources & evidence
- ORD record
- ord-dafa8f99e761496aa3f11455300e714c
- Source dataset
- uspto-grants-2002_05
- Patent number
- US06387892B1
Reaction notes
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