Acetyl chloride → 1,1-Dimethylethyl 2-acetyl-2,3-dihydrospiro[isoquinoline-4(1H),4′-piperidine]-1′-carboxylate

HRID 251483Notes

Reaction equation

HRID 251483 reaction equation
[N:1]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:6][CH2:5][C:4]2([C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9][NH:8][CH2:7]2)[CH2:3][CH2:2]1.[C:23](Cl)(=[O:25])[CH3:24].C(N(CC)CC)C>ClCCl>[C:23]([N:8]1[CH2:7][C:4]2([CH2:3][CH2:2][N:1]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:6][CH2:5]2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)(=[O:25])[CH3:24]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 46942140tert-Butyl 2,3-dihydro-1H,1'H-spiro[isoquinoline-4,4'-piperidine]-1'-carboxylate

Product 1

HCID 572265661,1-Dimethylethyl 2-acetyl-2,3-dihydrospiro[isoquinoline-4(1H),4′-piperidine]-1′-carboxylateYield 126.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

tert-Butyl 2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-carboxylate 6a (2.128 g, 6.28 mmol) was dissolved in anhydrous dichloromethane (30 mL), cooled in an ice-H2O bath and treated dropwise with a solution of acetyl chloride (518 mg, 6.59 mmol) in anhydrous dichloromethane (5 mL). The reaction was then treated dropwise with a solution of triethylamine (1.335 g, 13.2 mmol) in anhydrous dichloromethane (5 mL). The reaction was stirred in the ice-H2O bath for 15 minutes, then diluted with dichloromethane (100 mL), washed with H2O, saturated NaHCO3 (3×), saturated brine, dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure to afford crude tert-butyl 2-acetyl-2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-carboxylate 6b as a colorless oil (2.732 g, quantitative yield). LC/MS m/z [M+H]+ 345.2 retention time 2.98 min (10-99% CH3CN—H2O gradient, with 0.05% TFA, 5 min).

Workup

  1. temperaturecooled in an ice-H2O bath
  2. washwashed with H2O, saturated NaHCO3 (3×), saturated brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-0853da871f044f7b9fea1cf1dd9420af
Source dataset
uspto-grants-2011_01
Patent number
US07863449B2

Reaction notes

Loading…