(R)-5-Bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-3,4-dihydroisoquinoline → (1S,3R)-5-Bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline

HRID 1854554Notes

Reaction equation

HRID 1854554 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][C@H:5]([CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[N:6]=[CH:7]2.[CH3:21][Mg]Cl>C(OCC)C>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][C@H:5]([CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:15])[CH3:16])[NH:6][C@H:7]2[CH3:21]

Participants

4

Reactant 2

HCID 123546513(R)-5-Bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-3,4-dihydroisoquinoline2×HCID 178418332HCID 178418332, compound

Product 1

HCID 118998349(1S,3R)-5-Bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinolineYield 106.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

Dissolve (3R)-5-bromo-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3,4 dihydroisoquinoline (3.4 g, 9.59 mmol) in diethyl ether (160 mL). Cool to −78° C. on a dry ice-acetone bath. Add methylmagnesium chloride (26.9 mL, 80.6 mmol, 3M in THF) dropwise. Warm the reaction mixture slowly to room temperature and stir overnight. Quench with saturated ammonium chloride solution slowly. Extract with dichloromethane and dry over sodium sulfate, filter, and concentrate under reduced pressure. Combine with the crude product from a substantially same reaction run with 1.73 mmol of (3R)-5-bromo-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3,4 dihydroisoquinoline. Purify the combined residues by silica gel chromatography eluting with ethyl acetate: hexanes (5-65% gradient) to give the title compound (3.78 g, 10.2 mmol). MS (m/z): 370 (M+1).

Workup

  1. temperatureWarm the reaction mixture slowly to room temperature
  2. customQuench with saturated ammonium chloride solution slowly
  3. extractionExtract with dichloromethane
  4. dry with materialdry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure
  7. customCombine with the crude product from a substantially same reaction
  8. customPurify the combined residues by silica gel chromatography
  9. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-35bc23e25d14484c9616c684f500e39a
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

Loading…