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

HRID 242059Notes

Reaction equation

HRID 242059 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>[F:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2([C:14]3[C:23]4[C:18](=[CH:19][CH:20]=[C:21]([O:24][CH2:26][CH2:27][NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:22]=4)[CH2:17][CH2:16][N:15]=3)[CH2:13][CH2:12][CH2:11]2)=[CH:8][CH:9]=1

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.

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

Sources & evidence

ORD record
ord-eba548dd14f4490cb9ef73b52c4fbc99
Source dataset
uspto-grants-2014_02
Patent number
US08653100B2

Reaction notes

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