4-Methylmorpholine → HCID 86684768, compound

HRID 579159Notes

Reaction equation

HRID 579159 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN([C:25]([O:29][N:30]1N=NC2C=CC=N[C:31]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.CNOC.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:8][C:9](=[O:10])[NH:11][C@H:12]([CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[C:13](=[O:15])[N:30]([O:29][CH3:25])[CH3:31])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14510026(2R)-{[(Benzyloxy)carbonyl]amino}(cyclohexyl)acetic acid

Product 1

HCID 86684768HCID 86684768, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (R)-benzyloxycarbonylamino-cyclohexyl-acetic acid (25 g, 88 mmol) in DMF (100 mL) at −10° C. was added HATU (36.7 g, 96 mmol, 1.0 equiv) followed by N,O-dimethyl hydroxyamine HCl salt (10.3 g, 105 mmol, 1.2 equiv). To this solution was then slowly added N-methyl morpholine (28.9 mL, 263 mmol, 3.0 equiv). The internal temperature was carefully monitored. During the addition, the internal temperature rose to 0° C. The solution was stirred at 0° C. for 2 hours after which the solution was diluted with EtOAc (500 mL) and washed with sat. aq. NaHCO3 solution, water, 1.0 N aq. HCl solution and brine. The organic layer was dried over Na2SO4 and the solvent including DMF was removed under vacuum. The residue was diluted with EtOAc and the solution was washed with water, brine, dried (MgSO4) and concentrated to give product [(R)-Cyclohexyl-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid benzyl ester 26 g (yield 90%).

Workup

  1. additionDuring the addition
  2. customrose to 0° C
  3. washwashed with sat. aq. NaHCO3 solution, water, 1.0 N aq. HCl solution and brine
  4. dry with materialThe organic layer was dried over Na2SO4
  5. customwas removed under vacuum
  6. additionThe residue was diluted with EtOAc
  7. washthe solution was washed with water, brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-25901e1eecd14506ba7cc989d7f28595
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

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