Potassium Carbonate → HCID 58847236, compound

HRID 1966317Notes

Reaction equation

HRID 1966317 reaction equation
ClC(O[CH:5](Cl)[CH3:6])=O.[CH2:8]([N:15]1C[C@H](C)O[C@H](C)[CH2:16]1)[C:9]1C=CC=[CH:11][CH:10]=1.C(N(CC)C(C)C)(C)C.[C:32]([O-:35])([O-])=O.[K+].[K+].F[C:39]1[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][C:40]=1[CH:41]=[O:42].CN(C)CCNC>C(Cl)Cl>[CH2:5]([C@H:32]1[O:35][C@@H:9]([CH2:10][CH3:11])[CH2:8][N:15]([C:39]2[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][C:40]=2[CH:41]=[O:42])[CH2:16]1)[CH3:6]

Participants

8

Reactant 6

HCID 11430Potassium CarbonateHCID 673381,2-Ethanediamine, N1,N1,N2-trimethyl-HCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 27347702-Fluoro-5-nitrobenzaldehydeHCID 98372214-benzyl-cis-2,6-dimethylmorpholine

Product 1

HCID 58847236HCID 58847236, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloroethyl chloroformate (2.18 mL, 20 mmol, Aldrich) is added to a solution of 4-benzyl-cis-2,6-dimethylmorpholine in CH2Cl2 (45 mL) with stirring in an ice bath. The solution is allowed to warm to room temperature and stirred for 21 hours. The solvent is removed by rotary evaporation and the residue is dissolved in methanol (25 mL). This solution was heated to reflux for 3 hours and the methanol is removed by rotary evaporation. The product is dissolved in CH3CN (40 mL) and treated with N,N-diisopropylethylamine (2.0 mL, 11.5 mmol, Aldrich). K2CO3 (1.5 g, 11 mmol, Mallinkrodt) and 2-fluoro-5-nitrobenzaldehyde (1.9 g, 1.13 mmol, Oakwood) is added and the mixture is heated at 60° C. for 21 hours. N,N,N′-trimethylethylenediamine (0.4 mL) is added and the reaction is stirred an additional 45 minutes @ 60° C. The mixture is filtered and the solvent is removed by rotary evaporation. The residue is taken up in CH2Cl2 (200 mL) and washed 2× with 1.0 M HCl, 1× with saturated NaHCO3 and 1× with brine (150 mL each). The organic layer is dried over Na2SO4 and filtered. The solvent is removed by rotary evaporation and the product is purified on a Biotage Flash 40M+ using a 15% EtOAc in heptane as eluent. The product containing fractions are pooled and the solvent is removed by rotary evaporation. The product is dried under vacuum yielding a yellow solid.

Workup

  1. stirringstirred for 21 hours
  2. customThe solvent is removed by rotary evaporation
  3. dissolutionthe residue is dissolved in methanol (25 mL)
  4. temperatureThis solution was heated
  5. temperatureto reflux for 3 hours
  6. customthe methanol is removed by rotary evaporation
  7. dissolutionThe product is dissolved in CH3CN (40 mL)
  8. temperaturethe mixture is heated at 60° C. for 21 hours
  9. stirringthe reaction is stirred an additional 45 minutes @ 60° C
  10. filtrationThe mixture is filtered
  11. customthe solvent is removed by rotary evaporation
  12. washwashed 2× with 1.0 M HCl, 1× with saturated NaHCO3 and 1× with brine (150 mL each)
  13. dry with materialThe organic layer is dried over Na2SO4
  14. filtrationfiltered
  15. customThe solvent is removed by rotary evaporation
  16. customthe product is purified on a Biotage Flash 40M+
  17. additionThe product containing fractions
  18. customthe solvent is removed by rotary evaporation
  19. customThe product is dried under vacuum
  20. customyielding a yellow solid

Sources & evidence

ORD record
ord-b04b9285b0514723824b1630a320a258
Source dataset
uspto-grants-2013_04
Patent number
US08420646B2

Reaction notes

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