Sodium hydride → tert-Butyl[2-({1-[1-(4-fluorophenyl)cyclobutyl]-3,4-dihydroisoquinolin-7-yl}oxy)ethyl]carbamate

HRID 1850839Notes

Reaction equation

HRID 1850839 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([C:14]3[C:23]4[C:18](=[CH:19][CH:20]=[C:21]([OH:24])[CH:22]=4)[CH2:17][CH2:16][N:15]=3)[CH2:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1.Br[CH2:26][CH2:27][NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32]>CCCCCC.CN(C)C=O>[C:31]([O:30][C:29](=[O:35])[NH:28][CH2:27][CH2:26][O:24][C:21]1[CH:22]=[C:23]2[C:18]([CH2:17][CH2:16][N:15]=[C:14]2[C:10]2([C:7]3[CH:6]=[CH:5][C:4]([F:3])=[CH:9][CH:8]=3)[CH2:13][CH2:12][CH2:11]2)=[CH:19][CH:20]=1)([CH3:34])([CH3:33])[CH3:32]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 582463501-[1-(4-Fluorophenyl)cyclobutyl]-3,4-dihydroisoquinolin-7-ol

Product 1

HCID 70258703tert-Butyl[2-({1-[1-(4-fluorophenyl)cyclobutyl]-3,4-dihydroisoquinolin-7-yl}oxy)ethyl]carbamate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolvent

Procedure

Sodium hydride (0.626 g, 15.64 mmol, 60% suspension in mineral oil) was washed under dry conditions under nitrogen atmosphere with n-hexane. Dimethylformamide (20 mL) was added followed by 1-[1-(4-fluorophenyl)cyclobutyl]-3,4-dihydroisoquinolin-7-ol (2.1 g, 7.11 mmol) under stirring. After the exothermic reaction had ceased stirring was continued at room temperature for 1 h before tert-butyl (2-bromoethyl)carbamate (4.78 g, 21.33 mmol) was added dropwise as a solution in dimethylformamide (10 mL). The reaction mixture was stirred at room temperature over night. The solvent was evaporated in vacuo. Ice water was added (60 mL) and the aqueous phase was extracted with ethyl acetate. The combined organic layers were dried (MgSO4) and the solvent was evaporated in vacuo. The crude product was purified by flash chromatography (silica, dichloromethane:methanol=100:1). Yield: 2.5 g (5.7 mmol, 36%).

Workup

  1. customAfter the exothermic reaction
  2. stirringhad ceased stirring
  3. stirringThe reaction mixture was stirred at room temperature over night
  4. customThe solvent was evaporated in vacuo
  5. additionIce water was added (60 mL)
  6. extractionthe aqueous phase was extracted with ethyl acetate
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. customthe solvent was evaporated in vacuo
  9. customThe crude product was purified by flash chromatography (silica, dichloromethane:methanol=100:1)

Sources & evidence

ORD record
ord-b2f1fad966b749d48994aa2adc97baa1
Source dataset
uspto-grants-2015_02
Patent number
US08957089B2

Reaction notes

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