4-Methylmorpholine → HCID 9823474, compound

HRID 1167386Notes

Reaction equation

HRID 1167386 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C@@H:10]([CH3:14])[C:11]([O-:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.C1(C)C(S(O)(=O)=O)=CC=CC=1.[NH2:41][CH2:42][C@@H:43]([CH2:54][CH:55]([CH3:57])[CH3:56])[C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45]>C1COCC1.CN(C=O)C>[C:1]([O:5][C:6]([NH:8][CH2:9][C@@H:10]([CH3:14])[C:11]([NH:41][CH2:42][C@@H:43]([CH2:54][CH:55]([CH3:57])[CH3:56])[C:44]([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45])=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 40425078HCID 40425078, compoundHCID 86590212HCID 86590212, compound

Product 1

HCID 9823474HCID 9823474, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (2R)-3-(tert-butoxy)carbonylamino-2-methylpropanoate (0.81 g, 4.0 mmol) in THF (20 ml) was cooled under Ar to −15° and successively treated with NMM (0.46 ml, 4.2 mmol), isobutyl chloroformate (0.55 ml, 4.2 mmol) and, after stirring for 5 min, a precooled solution of benzyl (2R)-2-aminomethyl4methylpentanoate toluenesulfonate ((2),1.79 g, 4.4 mmol) and NMM (0.48 ml, 4.4 mmol) in DMF (10 ml). The mixture was allowed to warm to r.t. over a period of 2 h and stirring was continued for further 2 h. The solvent was removed under reduced pressure, the residue dissolved in AcOEt and washed with 10% aq. citric acid (3×), sat. aq. K2CO3 (3×), H2and sat. aq. NaCl soln. The org. phase was dried (MgSO4) and evaporated. Purification by FC (hexane/AcOEt 2:1) yielded The title compound (1.46 g, 87%): White solid.1H-NMR (200 MHz, CDCl3): 0.92 (d, J=5.5, 6H, CH(CH3)2); 1.05 (d, J=6.5, 3H, CHRCH3); 1.23-1.40 (m,1H, CH(CH3)2); 1.44 (s, 9H, C(CH3)3); 1.52-1.77 (m, 2H, CH2CH(CH3)2); 2.30-2.50 (m, 1H, COCHR); 2.68-2.85 (m, 1H, COCHR); 3.08-3.42 (m, 3H, 3 NCH); 3.45-3.60 (m, 1H, NCH); 5.04 (br.,1H, NHCOCHR); 5.16 (s, 2H, CH2Ph); 5.90 (br.,1H, NHCOOtBu); 7.10-7.28 (m, 5H, H-arom.).

Workup

  1. stirringstirring
  2. waitwas continued for further 2 h
  3. customThe solvent was removed under reduced pressure
  4. dissolutionthe residue dissolved in AcOEt
  5. washwashed with 10% aq. citric acid (3×), sat. aq. K2CO3 (3×), H2and sat. aq. NaCl soln
  6. dry with materialphase was dried (MgSO4)
  7. customevaporated
  8. customPurification by FC (hexane/AcOEt 2:1)

Sources & evidence

ORD record
ord-7d16b7f81d57415c9361ef12213e9c0f
Source dataset
uspto-grants-2003_09
Patent number
US06617425B1

Reaction notes

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