4-Methylmorpholine → HCID 58857939, compound

HRID 1162822Notes

Reaction equation

HRID 1162822 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:22][NH:23][O:24][CH3:25].CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[CH2:9][C:10]([N:23]([O:24][CH3:25])[CH3:22])=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 39382716HCID 39382716, compound

Product 1

HCID 58857939HCID 58857939, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of N-(tert-butoxycarbonyl)-N-(4-fluorobenzyl)glycine (10.5 g, 37.2 mmol) in CH2Cl2 (37 mL) was added N,O-dimethylhydroxylamine hydrochloride (3.62 g, 37.2 mmol). The resulting suspension was treated with N-methylmorpholine (4.08 mL, 37.2 mmol) and cooled to 0° C. The mixture was then treated with a 1 M solution of N,N′-dicyclohexylcarbodiimide in CH2Cl2 (37.2 mL, 37.2 mmol) and was then allowed to warm to ambient temperature under inert atmosphere. After stirring for 66 h, the mixture was filtered, washing the solid residue with excess CH2Cl2. The filtrate was concentrated in vacuo and resuspended in EtOAc. After stirring for 1 h, the mixture was filtered, washing the solids with excess EtOAc. The filtrate was again concentrated in vacuo to give an orange oil. Purification by silica gel chromatography (20% to 60% EtOAc/hexanes) afforded the title compound as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.27-7.20 (m, 2H), 7.03-7.01 (m, 2H), 4.52 (d, J=13.6 Hz, 2H), 4.09 (s, 1H), 3.95 (s, 1H), 3.63 (d, J=20.4 Hz, 3H), 3.18 (s, 3H), 1.47 (s, 9H). ES MS (M+1)=327.17.

Workup

  1. temperatureto warm to ambient temperature under inert atmosphere
  2. filtrationthe mixture was filtered
  3. washwashing the solid residue with excess CH2Cl2
  4. concentrationThe filtrate was concentrated in vacuo
  5. stirringAfter stirring for 1 h
  6. filtrationthe mixture was filtered
  7. washwashing the solids with excess EtOAc
  8. concentrationThe filtrate was again concentrated in vacuo
  9. customto give an orange oil
  10. customPurification by silica gel chromatography (20% to 60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-7416bfe1b22f42169b7ea994af03846c
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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