Imidazole → [(3R)-5-Bromo-1,2,3,4-tetrahydroisoquinolin-3-YL]methoxy-tert-butyl-dimethyl-silane

HRID 1854551Notes

Reaction equation

HRID 1854551 reaction equation
[C:1]([Si:5]([CH3:8])([CH3:7])Cl)([CH3:4])([CH3:3])[CH3:2].[Br:9][C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[CH2:12][C@H:13]([CH2:20][OH:21])[NH:14][CH2:15]2.N1C=CN=C1.[Cl-].[NH4+]>CN(C)C1C=CN=CC=1.ClCCl.C(OC)(C)(C)C.CN(C)C=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:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:8])[CH3:7])[NH:14][CH2:15]2

Participants

9

Reactant 4

HCID 795ImidazoleHCID 25517Ammonium ChlorideHCID 28928tert-Butyldimethylsilyl chlorideHCID 117720341(R)-(5-Bromo-1,2,3,4-tetrahydroisoquinolin-3-yl)methanol

Product 1

HCID 123224990[(3R)-5-Bromo-1,2,3,4-tetrahydroisoquinolin-3-YL]methoxy-tert-butyl-dimethyl-silaneYield 91.4%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
10 °C

Procedure

Add tert-butyldimethylchlorosilane (193.7 g, 1.29 mol) to a mixture of [(3R)-5-bromo-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol (148.9 g, 0.58 mol), 1H-imidazole (202.9 g, 2.92 mol), 4-dimethylaminopyridine (0.72 g, 5.84 mmol) and N,N-dimethylformamide (1.04 L) in dichlormethane (2.61 L) at 20° C. and stir in an appropriate vessel. After 3 hours, cool the mixture to 10° C. and add saturated aqueous ammonium chloride solution (1.3 L). Extract the aqueous with dichloromethane and wash the combined organic extracts with brine (2×2 L), dry over anhydrous sodium sulfate and concentrate under reduced pressure to give a residue. Dissolve the residue in methyl tert-butyl ether (1.5 L) and wash with brine (2×1 L). Dilute the organic phase with toluene (5 L) and concentrate under reduced pressure to give a residue. Add toluene (2.6 L) to the residue and concentrate under reduced pressure to give the title compound (210 g, 0.53 mol). MS (m/z). 356(M+1 (79Br)), 358(M+1 (81Br)).

Workup

  1. extractionExtract the aqueous with dichloromethane
  2. washwash the combined organic extracts with brine (2×2 L)
  3. dry with materialdry over anhydrous sodium sulfate
  4. concentrationconcentrate under reduced pressure
  5. customto give a residue
  6. washwash with brine (2×1 L)
  7. additionDilute the organic phase with toluene (5 L)
  8. concentrationconcentrate under reduced pressure
  9. customto give a residue
  10. concentrationAdd toluene (2.6 L) to the residue and concentrate under reduced pressure

Sources & evidence

ORD record
ord-6ed71016e02a4c759678c5114fbdbbf9
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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