4-Methylmorpholine → HCID 86757664, compound

HRID 2269361Notes

Reaction equation

HRID 2269361 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][C@H:10]([C@@H:14]([NH:18][O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[CH2:15][CH2:16][CH3:17])[C:11]([OH:13])=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O[CH:30]=[O:31])(=O)C.[F:32][C:33]1[C:38](O)=[C:37]([F:40])[C:36]([F:41])=[C:35]([F:42])[C:34]=1[F:43].CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1>N1C=CC=CC=1>[C:1]1([CH2:7][CH2:8][CH2:9][C@H:10]([C@@H:14]([N:18]([CH:30]=[O:31])[O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[CH2:15][CH2:16][CH3:17])[C:11]([O:13][C:38]2[C:37]([F:40])=[C:36]([F:41])[C:35]([F:42])=[C:34]([F:43])[C:33]=2[F:32])=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 13041PentafluorophenolHCID 75269Acetic-formic anhydrideHCID 57069188HCID 57069188, compound

Product 1

HCID 86757664HCID 86757664, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2R,3S)-2-(3-phenyl-1-propyl)-3-(2-tetrahydropyranyloxyamino)hexanoic acid (0.93 g, 2.66 mmol) in pyridine (2 mL) at 0° C. is added formic acetic anhydride (0.4 mL). The resulting solution is stirred at 0° C. for 1 h, concentrated in vacuo, and diluted with 11 mL of EtOAc. To the solution of crude acid is added pentafluorophenol (0.51 g, 2.79 mmol), NMM (0.28 g, 2.79 mmol) and dicyclohexylcarbodiimide (0.58 g, 2.79 mmol). The resulting solution is stirred at 23° C. for 20 h and is filtered. The filtrate is washed with 1 N hydrochloric acid, 1 M aqueous sodium carbonate solution, and saturated aqueous sodium chloride solution. The organic layer is dried over magnesium sulfate, concentrated, and purified by silica gel chromatography (elution with 9:1 hexanes-EtOAc) to provide pentafluorophenyl (2R,3S)-2-(3-phenyl-1-propyl)-3-(formyl-2-tetrahydropyranyloxyamino)hexanoate as an oil (0.84 g, 58% yield).

Workup

  1. concentrationconcentrated in vacuo
  2. additiondiluted with 11 mL of EtOAc
  3. stirringThe resulting solution is stirred at 23° C. for 20 h
  4. filtrationis filtered
  5. washThe filtrate is washed with 1 N hydrochloric acid, 1 M aqueous sodium carbonate solution, and saturated aqueous sodium chloride solution
  6. dry with materialThe organic layer is dried over magnesium sulfate
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography (elution with 9:1 hexanes-EtOAc)

Sources & evidence

ORD record
ord-47f432e8a8934f8b8d4a832498992289
Source dataset
uspto-grants-2001_12
Patent number
US06329400B1

Reaction notes

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