4-Methylmorpholine → HCID 57571330, compound

HRID 1423898Notes

Reaction equation

HRID 1423898 reaction equation
[C:1]([NH:8][C@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[N:21]1[CH2:26][CH2:25]O[CH2:23][CH2:22]1.ClC(OCC(C)C)=O.N1CCCC1>C1COCC1>[O:19]=[C:17]([N:21]1[CH2:26][CH2:25][CH2:23][CH2:22]1)[C@@H:9]([NH:8][C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7])[CH2:10][C:11]1[CH:12]=[CH:13][N:14]=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 31268PyrrolidineHCID 62365Isobutyl chloroformateHCID 7020844(2S)-2-(((tert-butoxy)carbonyl)amino)-3-(pyridin-4-yl)propanoic acid

Product 1

HCID 57571330HCID 57571330, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of N-Boc-(2S)-3-(pyridin-4-yl)alanine (500 mg, 1.9 mmol) in THF (12 mL) was added N-methylmorpholine (200 μL, 1.9 mmol) and the solution was stirred for 5 min, cooled at −15° C. and treated dropwise with isobutyl chloroformate (249 μL, 1.9 mmol). The mixture was stirred for 10 min and pyrrolidine (1.08 g, 15.2 mmol) was added and allowed to warm to 25° C. with stirring for 3 h. The solvent were removed under reduced pressure and the residue was partitioned between EtOAc and NaH2PO4 pH=7.2. The aqueous layer was discarded and the organic layer was washed with aqueous saturated NaHCO3, dried over Na2SO4, filtered and evaporated. The resulting solid was purified by column chromatography (SiO2) with a gradient of 0% to 10% [v/v] MeOH in EtOAc to give tert-butyl(S)-1-oxo-3-(pyridin-4-yl)-1-(pyrrolidin-1-yl)propan-2-ylcarbamate EBE 06190 (167 mg, 28% yield) as a white solid.

Workup

  1. stirringThe mixture was stirred for 10 min
  2. temperatureto warm to 25° C.
  3. stirringwith stirring for 3 h
  4. customThe solvent were removed under reduced pressure
  5. customthe residue was partitioned between EtOAc and NaH2PO4 pH=7.2
  6. washthe organic layer was washed with aqueous saturated NaHCO3
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe resulting solid was purified by column chromatography (SiO2) with a gradient of 0% to 10% [v/v] MeOH in EtOAc

Sources & evidence

ORD record
ord-b827f029e5294703af908346d6783c4a
Source dataset
uspto-grants-2015_01
Patent number
US08927589B2

Reaction notes

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