2,6-Lutidine → (2R)-N-cyclopropyl-N-{(1R)-1-[4-(3-methoxypropoxy)-1-benzofuran-6-yl]ethyl}morpholine-2-carboxamide

HRID 922411Notes

Reaction equation

HRID 922411 reaction equation
[CH:1]1([N:4]([CH:20]([C:22]2[CH:30]=[C:29]([O:31][CH2:32][CH2:33][CH2:34][O:35][CH3:36])[C:25]3[CH:26]=[CH:27][O:28][C:24]=3[CH:23]=2)[CH3:21])[C:5]([C@@H:7]2[O:12][CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8]2)=[O:6])[CH2:3][CH2:2]1.N1C(C)=CC=CC=1C.C[Si](OS(C(F)(F)F)(=O)=O)(C)C.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[CH:1]1([N:4]([C@@H:20]([C:22]2[CH:30]=[C:29]([O:31][CH2:32][CH2:33][CH2:34][O:35][CH3:36])[C:25]3[CH:26]=[CH:27][O:28][C:24]=3[CH:23]=2)[CH3:21])[C:5]([C@@H:7]2[O:12][CH2:11][CH2:10][NH:9][CH2:8]2)=[O:6])[CH2:3][CH2:2]1.[CH:1]1([N:4]([C@H:20]([C:22]2[CH:30]=[C:29]([O:31][CH2:32][CH2:33][CH2:34][O:35][CH3:36])[C:25]3[CH:26]=[CH:27][O:28][C:24]=3[CH:23]=2)[CH3:21])[C:5]([C@@H:7]2[O:12][CH2:11][CH2:10][NH:9][CH2:8]2)=[O:6])[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 79372,6-LutidineHCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 68309685tert-butyl (2R)-2-[(cyclopropyl{1-[4-(3-methoxypropoxy)-1-benzofuran-6-yl]ethyl}amino)carbonyl]morpholine-4-carboxylate

Product 2

HCID 66548854(2R)-N-cyclopropyl-N-{(1R)-1-[4-(3-methoxypropoxy)-1-benzofuran-6-yl]ethyl}morpholine-2-carboxamideHCID 68308680(2R)-N-cyclopropyl-N-{(1S)-1-[4-(3-methoxypropoxy)-1-benzofuran-6-yl]ethyl}morpholine-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of tert-butyl (2R)-2-[(cyclopropyl{1-[4-(3-methoxypropoxy)-1-benzofuran-6-yl]ethyl}amino)carbonyl]morpholine-4-carboxylate (200 mg) and 2,6-lutidine (0.142 mL) in chloroform (4 mL) was added trimethylsilyltriflate (0.180 mL) under ice-cooling, and the mixture was stirred at the same temperature for 30 minutes. Then, thereto was added aqueous saturated sodium hydrogen carbonate solution under ice-cooling, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol/ammonia water=200/2/1) to give (2R)-N-cyclopropyl-N-{(1R)-1-[4-(3-methoxypropoxy)-1-benzofuran-6-yl]ethyl}morpholine-2-carboxamide [Ex(1-1)] (12.5 mg) and (2R)-N-cyclopropyl-N-{(1S)-1-[4-(3-methoxypropoxy)-1-benzofuran-6-yl]ethyl}morpholine-2-carboxamide [Ex(1-2)] (20.2 mg) as a colorless oil.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated saline
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (eluent: chloroform/methanol/ammonia water=200/2/1)

Sources & evidence

ORD record
ord-a3103d884f784b4f8af3e58c77ae03f6
Source dataset
uspto-grants-2016_03
Patent number
US09278944B2

Reaction notes

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