4-Methylmorpholine → Tert-butyl[2-(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]carbamate

HRID 2383017Notes

Reaction equation

HRID 2383017 reaction equation
Cl.[CH:2]1([CH:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][CH2:10][NH:9]2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C(Cl)(=O)C(C)(C)C.CN1CCOCC1.[C:32]([O:36][C:37]([NH:39][CH2:40][C:41](O)=[O:42])=[O:38])([CH3:35])([CH3:34])[CH3:33]>C(Cl)Cl.O>[C:32]([O:36][C:37](=[O:38])[NH:39][CH2:40][C:41]([N:9]1[CH2:10][CH2:11][C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:8]1[CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1)=[O:42])([CH3:35])([CH3:33])[CH3:34]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62493Pivaloyl chlorideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 675358401-Cyclohexyl-1,2,3,4-tetrahydroisoquinoline hydrochloride

Product 1

HCID 68250253Tert-butyl[2-(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]carbamateYield 100.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

1-cyclohexyl-1,2,3,4-tetrahydroisoquinoline hydrochloride (1.00 g) was dissolved in methylene chloride (20 mL), and pivaloyl chloride (0.98 mL) and 4-methylmorpholine (2.2 mL) were added thereto under ice-cooling. The reaction liquid was stirred at room temperature for 30 minutes and then ice-cooled, and [(tert-butoxycarbonyl)amino]acetic acid (1.54 g) was added thereto. The reaction liquid was stirred at room temperature for 14 hours and then water was added thereto, followed by extraction with chloroform. The extract was washed with saturated brine, and then dried over magnesium sulfate. The solvent was evaporated and the resulting residue was purified by silica gel column chromatography (chloroform-MeOH) to obtain tert-butyl[2-(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]carbamate (1.49 g).

Workup

  1. temperatureunder ice-cooling
  2. customThe reaction liquid
  3. temperatureice-cooled
  4. customThe reaction liquid
  5. stirringwas stirred at room temperature for 14 hours
  6. extractionfollowed by extraction with chloroform
  7. washThe extract was washed with saturated brine
  8. dry with materialdried over magnesium sulfate
  9. customThe solvent was evaporated
  10. customthe resulting residue was purified by silica gel column chromatography (chloroform-MeOH)

Sources & evidence

ORD record
ord-4e31b68b89a2401bbc988e2a880062c6
Source dataset
uspto-grants-2012_09
Patent number
US08263607B2

Reaction notes

Loading…