Cesium carbonate → Tert-butyl 4-{[6-bromo-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-4-yl]sulfanyl}piperidine-1-carboxylate

HRID 906457Notes

Reaction equation

HRID 906457 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][CH:6]=[C:5]2[S:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.Br[CH2:28][C:29]([CH3:40])([CH3:39])[CH2:30][O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH2:23]([O:22][CH2:20][CH3:28])[CH3:26].[CH3:11][CH2:2][CH2:3][CH:4]([CH3:9])[CH3:5].[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:28][C:29]([CH3:40])([CH3:39])[CH2:30][O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:33])[CH3:34])[CH:6]=[C:5]2[S:13][CH:14]1[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 11780954(3-Bromo-2,2-dimethylpropoxy)(tert-butyl)dimethylsilaneHCID 67130258tert-Butyl 4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfanyl]piperidine-1-carboxylate

Product 2

HCID 21882825Ether isohexaneYield 25%HCID 67390931Tert-butyl 4-{[6-bromo-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-4-yl]sulfanyl}piperidine-1-carboxylateYield 96.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of tert-butyl 4-[(6-bromo-1-oxo-1,2-dihydroisoquinolin-4-yl)sulfanyl]piperidine-1-carboxylate (Example 58b, 0.353 g) in DMF (5 mL) was treated with (3-bromo-2,2-dimethylpropoxy)(tert-butyl)dimethylsilane (0.452 g) and cesium carbonate (0.785 g). The mixture was stirred at 80° C. for 16 h, then at 90° C. for 16 h. After cooling to room temperature the reaction mixture was partitioned between water (250 mL) and ethyl acetate (3×250 mL). The combined organics were washed with water (3×200 mL) and brine (3×100 mL), dried (MgSO4), filtered and concentrated. The crude product was dissolved in the minimum amount of DCM and purified (SiO2 chromatography, eluting first with isohexane, then 25% diethyl ether/isohexane) to afford the subtitle compound (0.248 g).

Workup

  1. waitat 90° C. for 16 h
  2. temperatureAfter cooling to room temperature the reaction mixture
  3. customwas partitioned between water (250 mL) and ethyl acetate (3×250 mL)
  4. washThe combined organics were washed with water (3×200 mL) and brine (3×100 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe crude product was dissolved in the minimum amount of DCM
  9. custompurified (SiO2 chromatography
  10. washeluting first with isohexane

Sources & evidence

ORD record
ord-e235ae7e823a40eebc48ef687dc9f235
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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