Di-tert-butyl dicarbonate → HCID 58641511, compound

HRID 2224088Notes

Reaction equation

HRID 2224088 reaction equation
[C:1]1([S:7]([C:10]2[CH:28]=[CH:27][C:13]3[N:14]([CH:20]4[CH2:25][CH2:24][N:23](C)[CH2:22][CH2:21]4)[CH2:15][C:16]([CH3:19])([CH3:18])[O:17][C:12]=3[CH:11]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClC(OC(Cl)C)=O.C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C>ClC(Cl)C>[C:1]1([S:7]([C:10]2[CH:28]=[CH:27][C:13]3[N:14]([CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)[CH2:15][C:16]([CH3:18])([CH3:19])[O:17][C:12]=3[CH:11]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 90495Di-tert-butyl dicarbonateHCID 5213051-Chloroethyl chloroformateHCID 58641516HCID 58641516, compound

Product 1

HCID 58641511HCID 58641511, compoundYield 75.5%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 7-benzenesulfonyl-2,2-dimethyl-4-(1-methyl-piperidin-4-yl)-3,4-dihydro-2H-benzo[1,4]oxazine (0.119 g., 0.298 mmol) in 3 mL dichloroethane was cooled to 0° C. and α-chloroethyl chloroformate (0.033 mL, 0.312 mmol) was added dropwise with stirring over 1 minute. The reaction mixture was refluxed for 18 hours, concentrated in vacuo, and the residue dissolved in 20 mL methanol and refluxed for 1 hour. The reaction mixture was concentrated in vacuo and a vacuum of 0.5 Torr was applied for 30 minutes. The resulting residue was dissolved in 35 mL THF, to which was added di-tert-butyldicarbonate (0.065 g., 0.300 mmol) and the reaction mixture was stirred for 72 hours at room temperature. The reaction mixture was then concentrated in vacuo and purified by flash chromatography (15% ethyl acetate in hexanes) to afford 0.087 g (75%) of 7-benzenesulfonyl-2,2-dimethyl-4-piperidin-4-yl-3,4-dihydro-2H-benzo[1,4]oxazine as a waxy solid. MS: 387, mp: 284.9-296.3° C. (as hydrochloride salt).

Workup

  1. temperatureThe reaction mixture was refluxed for 18 hours
  2. concentrationconcentrated in vacuo
  3. dissolutionthe residue dissolved in 20 mL methanol
  4. temperaturerefluxed for 1 hour
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. waita vacuum of 0.5 Torr was applied for 30 minutes
  7. dissolutionThe resulting residue was dissolved in 35 mL THF, to which
  8. stirringthe reaction mixture was stirred for 72 hours at room temperature
  9. concentrationThe reaction mixture was then concentrated in vacuo
  10. custompurified by flash chromatography (15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-481d548aa4d3474da1c7256287cfabd6
Source dataset
uspto-grants-2008_05
Patent number
US07378415B2

Reaction notes

Loading…