4-Methylmorpholine → HCID 69778246, compound

HRID 1279842Notes

Reaction equation

HRID 1279842 reaction equation
[C:1]([O:5][C:6](=[O:32])[CH2:7][C@H:8]([C:18]1[O:22][N:21]=[C:20]([C:23]([N:25]2[CH2:28][CH:27]([C:29]([OH:31])=[O:30])[CH2:26]2)=[O:24])[N:19]=1)[CH2:9][CH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:4])([CH3:3])[CH3:2].[CH3:33]N1CCOCC1.ClC(OCC(C)C)=O>ClCCl>[C:1]([O:5][C:6](=[O:32])[CH2:7][C@H:8]([C:18]1[O:22][N:21]=[C:20]([C:23]([N:25]2[CH2:28][CH:27]([C:29]([O:31][CH3:33])=[O:30])[CH2:26]2)=[O:24])[N:19]=1)[CH2:9][CH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 59074806HCID 59074806, compound

Product 1

HCID 69778246HCID 69778246, compoundYield 46.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1-[(5-{(1R)-1-[2-(tert-butoxy)-2-oxoethyl]-4-cyclohexylbutyl}-1,2,4-oxadiazol-3-yl)carbonyl]-3-azetidinecarboxylic acid (Preparation 41) (480 mg, 1.07 mmol) and N-methylmorpholine (130 μl, 1.17 mmol) in dichloromethane (10 ml) was cooled to 0° C. and then treated with isobutyl chloroformate (150 μl, 1.17 mmol). The mixture was stirred at 0° C. for 30 minutes then allowed to warm to room temperature over 1 hour. The mixture was quenched with methanol (5 ml) and the solvent removed under reduced pressure. The residue was partitioned between ethyl acetate and hydrochloric acid (1M). The combined organic layers 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:ethyl acetate (95:5) gradually changing to dichloromethane:ethyl acetate (90:10) to afford the title compound (230 mg)

Workup

  1. temperatureto warm to room temperature over 1 hour
  2. customThe mixture was quenched with methanol (5 ml)
  3. customthe solvent removed under reduced pressure
  4. customThe residue was partitioned between ethyl acetate and hydrochloric acid (1M)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:ethyl acetate (95:5)

Sources & evidence

ORD record
ord-342e6a5436ea40cb878941c42b28258e
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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