4-Methylmorpholine → HCID 10227051, compound

HRID 1279776Notes

Reaction equation

HRID 1279776 reaction equation
[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([N:22]3[CH2:27][CH2:26][CH:25]([C:28]4[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=4)[CH2:24][CH2:23]3)=[O:21])[N:16]=2)[CH2:11][C:12](O)=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:50][OH:51]>CN(C)C=O>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([N:22]3[CH2:27][CH2:26][CH:25]([C:28]4[CH:29]=[CH:30][N:31]=[CH:32][CH:33]=4)[CH2:24][CH2:23]3)=[O:21])[N:16]=2)[CH2:11][C:12]([NH:50][OH:51])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 443297Hydroxyamine hydrochlorideHCID 59909829HCID 59909829, compound

Product 1

HCID 10227051HCID 10227051, compoundYield 29.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (3R)-6-cyclohexyl-3-(3-{[4-(4-pyridinyl)-1-piperidinyl]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoic acid (Preparation 32) (311 mg, 0.68 mmol) and N-methylmorpholine (83 μl, 0.75 mmol) in N,N-dimethylformamide (15 ml) was cooled to 0° C., treated dropwise with isobutyl chloroformate (98 μl, 0.75 mmol) and the resulting solution was stirred at 0° C. for 45 minutes. Hydroxylamine hydrochloride (142 mg, 2.05 mmol) was then added followed by further N-methylmorpholine (226 μl, 2.05 mmol) and the mixture was stirred for 18 hours being allowed to warm to room temperature over this time. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate (50 ml) and water (50 ml). The layers were separated and the aqueous phase extracted with ethyl acetate (×2). The combined organic phases were washed with brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by HPLC to afford a residue that was partitioned between ethyl acetate and water. The organic phase was separated, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The residue was triturated with diethyl ether to yield the title compound as a white solid (94 mg).

Workup

  1. stirringthe mixture was stirred for 18 hours
  2. temperatureto warm to room temperature over this time
  3. customThe solvent was removed under reduced pressure
  4. customthe residue partitioned between ethyl acetate (50 ml) and water (50 ml)
  5. customThe layers were separated
  6. extractionthe aqueous phase extracted with ethyl acetate (×2)
  7. washThe combined organic phases were washed with brine
  8. dry with materialdried over anhydrous sodium sulphate
  9. filtrationfiltered
  10. customthe solvent removed under reduced pressure
  11. customThe residue was purified by HPLC
  12. customto afford a residue that
  13. customwas partitioned between ethyl acetate and water
  14. customThe organic phase was separated
  15. dry with materialdried over anhydrous sodium sulphate
  16. filtrationfiltered
  17. customthe solvent removed under reduced pressure
  18. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-e447a20bd37844e4bbb0a57445cb829f
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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