4-Methylmorpholine → HCID 21018571, compound

HRID 1744689Notes

Reaction equation

HRID 1744689 reaction equation
[Cl-:1].[CH:2]1([C:8]2([CH2:14][N:15]3[C:19]([CH3:21])([CH3:20])[CH2:18][O:17][C:16]3=[O:22])[CH2:13][CH2:12][NH2+:11][CH2:10][CH2:9]2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(OC([N:59]1[CH2:63][C@@H:62]([C:64]2[CH:69]=[CH:68][C:67]([F:70])=[CH:66][CH:65]=2)[C@@H:61]([C:71](O)=[O:72])[CH2:60]1)=O)(C)(C)C.N1CCCC1>C(Cl)Cl>[Cl-:1].[CH:2]1([C:8]2([CH2:14][N:15]3[C:19]([CH3:20])([CH3:21])[CH2:18][O:17][C:16]3=[O:22])[CH2:9][CH2:10][N:11]([C:71]([C@@H:61]3[C@H:62]([C:64]4[CH:69]=[CH:68][C:67]([F:70])=[CH:66][CH:65]=4)[CH2:63][NH2+:59][CH2:60]3)=[O:72])[CH2:12][CH2:13]2)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 31268PyrrolidineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 17980475HCID 17980475, compoundHCID 51557049HCID 51557049, compound

Product 1

HCID 21018571HCID 21018571, compoundYield 86.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 4-cyclohexyl-4-[(4,4-dimethyl-2-oxo-1,3-oxazolidin-3-yl)methyl]piperidinium chloride (150 mg; 0.4532 mmol) in methylene chloride (4.0 mL) was added N-methylmorpholine (183 mg; 0.2 mL). After 20 min, the following reagents were added sequentially: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (130 mg; 0.6798 mmol), 1-hydroxybenzotriazole (92 mg; 0.6798 mmol) and the product of step D (154 mg; 0.4985 mmol). The final reaction mixture was maintained at ambient temperature for 48 h. The reaction mixture was diluted with methylene chloride (100 mL) followed by washing the organic solution with saturated sodium bicarbonate and brine. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo to provide the crude N-BOC protected pyrrolidine that was purified on silica gel (50% ethyl acetate/hexane as the elution solvent). The crude N-BOC protected pyrrolidine was then dissolved in ethyl acetate (2 mL) followed by the addition of a saturated solution of hydrogen chloride in ethyl acetate (2 mL). The reaction mixture was maintained at ambient temperature for 2 h at which time the volatiles were removed in vacuo. The crude product was triturated to high purity with diethyl ether which furnished 204 mg of the title compound as a hydrochloride salt.

Workup

  1. additionthe following reagents were added sequentially
  2. customThe final reaction mixture
  3. washby washing the organic solution with saturated sodium bicarbonate and brine
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto provide the crude N-BOC
  8. customwas purified on silica gel (50% ethyl acetate/hexane as the elution solvent)
  9. dissolutionwas then dissolved in ethyl acetate (2 mL)
  10. additionfollowed by the addition of a saturated solution of hydrogen chloride in ethyl acetate (2 mL)
  11. temperatureThe reaction mixture was maintained at ambient temperature for 2 h at which time the volatiles
  12. customwere removed in vacuo
  13. customThe crude product was triturated to high purity with diethyl ether which

Sources & evidence

ORD record
ord-aa56b96d1fa74ec1b44f05c0859e1e3c
Source dataset
uspto-grants-2006_03
Patent number
US07015235B2

Reaction notes

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