Potassium Carbonate → HCID 58847022, compound

HRID 1966328Notes

Reaction equation

HRID 1966328 reaction equation
ClC(OC(Cl)C)=O.C([N:15]1[CH2:20][C@H:19]([CH3:21])[O:18][C@@H:17]([CH3:22])[CH2:16]1)C1C=CC=CC=1.C(N(CC)C(C)C)(C)C.C([O-])([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]>C(Cl)Cl>[CH3:22][C@@H:17]1[O:18][C@@H:19]([CH3:21])[CH2:20][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

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformateHCID 27347702-Fluoro-5-nitrobenzaldehydeHCID 11183342(2S,6S)-4-Benzyl-2,6-dimethylmorpholine

Product 1

HCID 58847022HCID 58847022, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloroethyl chloroformate (292 μL, 2.68 mmol, Aldrich) is added to a solution of (2S,6S)-4-benzyl-2,6-dimethylmorpholine (in CH2Cl2 (6 mL) with stirring in an ice bath. The solution is allowed to warm to room temperature and stirred for 2.5 hours. The solvent is removed by rotary evaporation and the residue is dissolved in methanol (6 mL). This solution is heated to reflux for 2.5 hours and the methanol is removed by rotary evaporation. The residue is dissolved in CH3CN (5 mL) and treated with N,N-diisopropylethylamine (244 μL, 1.4 mmol, Aldrich). K2CO3 (190 mg, 1.37 mmol, Mallinkrodt) and 2-fluoro-5-nitrobenzaldehyde (230 mg, 1.36 mmol, Oakwood) are added and the mixture is heated at 60° C. for 21 hours. The mixture is filtered and the solvent is removed by rotary evaporation. The residue is dissolved in CH2Cl2 (100 mL) and washed sequentially with water (75 mL) and brine (75 mL). The organic layer is purified on a Biotage Flash 25M+ using a 40% 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 syrup.

Workup

  1. stirringstirred for 2.5 hours
  2. customThe solvent is removed by rotary evaporation
  3. dissolutionthe residue is dissolved in methanol (6 mL)
  4. temperatureThis solution is heated
  5. temperatureto reflux for 2.5 hours
  6. customthe methanol is removed by rotary evaporation
  7. dissolutionThe residue is dissolved in CH3CN (5 mL)
  8. temperaturethe mixture is heated at 60° C. for 21 hours
  9. filtrationThe mixture is filtered
  10. customthe solvent is removed by rotary evaporation
  11. dissolutionThe residue is dissolved in CH2Cl2 (100 mL)
  12. washwashed sequentially with water (75 mL) and brine (75 mL)
  13. customThe organic layer is purified on a Biotage Flash 25M+
  14. additionThe product containing fractions
  15. customthe solvent is removed by rotary evaporation
  16. customThe product is dried under vacuum
  17. customyielding a yellow syrup

Sources & evidence

ORD record
ord-cd4cac9dc7154869b4161b052840383c
Source dataset
uspto-grants-2013_04
Patent number
US08420646B2

Reaction notes

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