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

HRID 1854550Notes

Reaction equation

HRID 1854550 reaction equation
FC(F)(F)C(O)=O.[Br:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH2:11][C@H:12]([CH2:19][OH:20])[NH:13][CH2:14]2.N1C=CN=C1.[C:26]([Si:30]([CH3:33])([CH3:32])Cl)([CH3:29])([CH3:28])[CH3:27].BrC1C=CC=C2C=1C[C@H](CO)N(C(OC(C)(C)C)=O)C2>ClCCl.CN(C)C1C=CN=CC=1>[Br:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH2:11][C@H:12]([CH2:19][O:20][Si:30]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:33])[CH3:32])[NH:13][CH2:14]2

Participants

8

Reactant 5

HCID 795ImidazoleHCID 6422Trifluoroacetic acid2×HCID 28928tert-Butyldimethylsilyl chlorideHCID 117720341(R)-(5-Bromo-1,2,3,4-tetrahydroisoquinolin-3-yl)methanolHCID 117722932tert-butyl (3R)-5-bromo-3-(hydroxymethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylate

Product 1

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

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Add trifluoroacetic acid (75.5 mL, 998.3 mmol) to solution of tert-butyl (3R)-5-bromo-3-(hydroxymethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylate (15.5 g, 45.3 mmol) in dichloromethane (226 mL) at room temperature. Stir 30 min and concentrate under reduced pressure. Dry under vacuum to give [(3R)-5-bromo-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol; 2,2,2-trifluoroacetic acid as a wet solid. Dissolve [(3R)-5-bromo-1,2,3,4-tetrahydroisoquinolin-3-yl]methanol; 2,2,2-trifluoroacetic acid in dichloromethane (753 mL). Add 1H-imidazole (51.3 g, 753 mmol), N,N-Dimethyl-4-pyridinamine (460 mg, 3.77 mmol), and t-butyldimethylchlorosilane (13.6 g, 90.4 mmol). Stir at room temperature overnight. Add saturated ammonium chloride solution and extract with dichloromethane. Dry the dichloromethane extracts over sodium sulfate, filter, and concentrate under reduced pressure. Combine with the crude product from a substantially same reaction run with 19.4 mmol of tert-butyl (3R)-5-bromo-3-(hydroxymethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylate. Purify the residue by silica gel chromatography eluting with ethyl acetate: hexanes (5-40% gradient) to give the title compound (14.3 g, 40.1 mmol). MS (m/z): 356 (M+1).

Workup

  1. extractionAdd saturated ammonium chloride solution and extract with dichloromethane
  2. dry with materialDry the dichloromethane
  3. filtrationfilter
  4. concentrationconcentrate under reduced pressure
  5. customCombine with the crude product from a substantially same reaction
  6. customPurify the residue by silica gel chromatography
  7. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-42fb0a8d70ac4813a876791917807282
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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