Methanol → (R)-5-Bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-3,4-dihydroisoquinoline

HRID 1854553Notes

Reaction equation

HRID 1854553 reaction equation
ClN1C(=O)CCC1=O.[Br:9][C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[CH2:12][C@H:13]([CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[NH:14][CH2:15]2.CO.O>O1CCCC1.[OH-].[K+]>[Br:9][C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[CH2:12][C@H:13]([CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:23])[CH3:24])[N:14]=[CH:15]2

Participants

7

Reactant 4

HCID 887MethanolHCID 962WaterHCID 31398ChlorosuccinimideHCID 123224990[(3R)-5-Bromo-1,2,3,4-tetrahydroisoquinolin-3-YL]methoxy-tert-butyl-dimethyl-silane

Product 1

HCID 123546513(R)-5-Bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-3,4-dihydroisoquinolineYield 96.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14797Potassium HydroxideSolvent

Procedure

Add N-chlorosuccinimide (106.7 g, 0.79 mol) to a solution of (3R)-5-bromo-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1,2,3,4-tetrahydroisoquinoline (220 g, 0.52 mol) in tetrahydrofuran (3.85 L) at 20° C. in an appropriate vessel and stir. After 30 minutes concentrate the mixture under reduced pressure and dissolve the residues in 5% w/w potassium hydroxide in methanol (2.2 L, 1.69 moles) and stir at 20° C. After 30 minutes, add the mixture to water (3 L) and extract three times with dichloromethane (3×1 L). Dry the combined organic extracts over anhydrous magnesium sulfate and concentrate under reduced pressure to give the title compound (210 g, 0.50 mol). MS (m/z): 354(M+1 (79Br)), 356(M+1 (81Br)).

Workup

  1. concentrationAfter 30 minutes concentrate the mixture under reduced pressure
  2. stirringstir at 20° C
  3. extractionextract three times with dichloromethane (3×1 L)
  4. dry with materialDry the combined organic extracts over anhydrous magnesium sulfate
  5. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-f4d5af27d1e241a0aa47371bfe30ff4b
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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