4-Methylmorpholine → HCID 10113858, compound

HRID 2182918Notes

Reaction equation

HRID 2182918 reaction equation
FC(F)(F)C(O)=O.[CH:8]1([CH2:14][CH2:15][CH2:16][C@@H:17]([C:22]2[O:26][N:25]=[C:24]([C:27]([N:29]3[CH2:34][CH2:33][CH:32]([N:35]([CH3:37])[CH3:36])[CH2:31][CH2:30]3)=[O:28])[N:23]=2)[CH2:18][C:19]([OH:21])=O)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:54][OH:55]>CN(C)C=O>[NH3:23].[CH:8]1([CH2:14][CH2:15][CH2:16][C@@H:17]([C:22]2[O:26][N:25]=[C:24]([C:27]([N:29]3[CH2:34][CH2:33][CH:32]([N:35]([CH3:37])[CH3:36])[CH2:31][CH2:30]3)=[O:28])[N:23]=2)[CH2:18][C:19]([NH:54][OH:55])=[O:21])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 443297Hydroxyamine hydrochlorideHCID 69778267(3R)-6-Cyclohexyl-3-(3-{[4-(dimethylamino)-1-piperidinyl]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoic Acid Trifluoroacetate

Product 2

HCID 222AmmoniaHCID 10113858HCID 10113858, compoundYield 8.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (3R)-6-cyclohexyl-3-(3-{[4-(dimethylamino)-1-piperidinyl]carbonyl}-1,2,4-oxadiazol-5yl) hexanoic acid trifluoroacetate (Preparation 26) (702 mg, 1.31 mmol) and N-methylmorpholine (159 μl, 1.45 mmol) in N,N-dimethylformamide (15 ml) was cooled to 0° C. and then treated with dropwise with isobutyl chloroformate (188 μl, 1.45 mmol). The resulting solution was stirred at 0° C. under a nitrogen atmosphere for 45 minutes. Hydroxylamine hydrochloride (274 mg, 3.94 mmol) was then added followed by further N-methylmorpholine (433 μl, 3.94 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 was dissolved in a saturated aqueous solution of sodium carbonate. The pH of the solution was adjusted to 9 by dropwise addition of acetic acid and the product was then 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 column chromatography on silica gel eluting with a gradient system of dichloromethane:methanol:0.88 ammonia (90:10:1) then dichloromethane:methanol:0.88 ammonia (80:20:2) to afford the title compound as an oil (23 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. dissolutionthe residue was dissolved in a saturated aqueous solution of sodium carbonate
  5. additionThe pH of the solution was adjusted to 9 by dropwise addition of acetic acid
  6. extractionthe product was then 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 column chromatography on silica gel eluting with a gradient system of dichloromethane

Sources & evidence

ORD record
ord-25d6e43858374c6c9df727a8f85c4f04
Source dataset
uspto-grants-2005_05
Patent number
US06897306B2

Reaction notes

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