4-Methylmorpholine → HCID 10223115, compound

HRID 2182938Notes

Reaction equation

HRID 2182938 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[CH2:25][CH:24]([N:26]([CH3:28])[CH3:27])[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.C[Si](C)(C)[O:46][NH2:47]>O1CCCC1.CO>[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[CH2:25][CH:24]([N:26]([CH3:28])[CH3:27])[CH2:23]3)=[O:21])[N:16]=2)[CH2:11][C:12]([NH:47][OH:46])=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 23378031(3R)-6-cyclohexyl-3-(3-{[3-(dimethylamino)-1-azetidinyl]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoic acid

Product 1

HCID 10223115HCID 10223115, compoundYield 86.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3R)-6-cyclohexyl-3-(3-{[3-(dimethylamino)-1-azetidinyl]carbonyl}-1,2,4-oxadiazol-5-yl)hexanoic acid (Preparation 76) (200 mg, 0.51 mmol) and N-methylmorpholine (112 μl, 1.00 mmol) in anhydrous tetrahydrofuran (15 ml) was cooled to 0° C., treated with isobutyl chloroformate (79 μl, 0.69 mmol) and stirred under a nitrogen atmosphere for 2 hours. O-(Trimethylsilyl)hydroxylamine (85 μl, 0.61 mmol) was added and the mixture was stirred for 18 hours, being allowed to warm to room temperature over this time. The mixture was then treated with methanol and stirred at room temperature for 2 hours. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (100 ml) and washed with water (2×25 ml) and brine (25 ml), dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure to afford the title compound as a foam (180 mg).

Workup

  1. stirringthe mixture was stirred for 18 hours
  2. stirringstirred at room temperature for 2 hours
  3. customThe solvent was removed under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate (100 ml)
  5. washwashed with water (2×25 ml) and brine (25 ml)
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-e834bb254b874ccaa9249e0609947d7b
Source dataset
uspto-grants-2005_05
Patent number
US06897306B2

Reaction notes

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