4-Methylmorpholine → (S)-benzyl 2-(2-morpholinoacetamido)propanoate

HRID 58886

Reaction equation

HRID 58886 reaction equation
C[N+]1(C2N=C(OC)N=C(OC)N=2)CCOCC1.[Cl-].CN1CCOCC1.[O:26]1[CH2:31][CH2:30][N:29]([CH2:32][C:33]([OH:35])=O)[CH2:28][CH2:27]1.Cl.[CH2:37]([O:44][C:45](=[O:49])[C@H:46]([CH3:48])[NH2:47])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CN(C=O)C.C(Cl)Cl>[O:26]1[CH2:27][CH2:28][N:29]([CH2:32][C:33]([NH:47][C@@H:46]([CH3:48])[C:45]([O:44][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[O:49])=[O:35])[CH2:30][CH2:31]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 4389684-Morpholineacetic acidHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 12210893L-Alanine, phenylmethyl ester, hydrochloride (1:1)

Product 1

HCID 117607729(S)-benzyl 2-(2-morpholinoacetamido)propanoateYield 49,908.602%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To DMTMM (76.1 g, 0.276 mol) and N-methylmorpholine (NMM; 32.9 mL, 0.300 mol) was added to a 0° C. solution of 2-morpholinoacetic acid (20.0 g, 0.138 mmol) and L-alanine benzyl ester hydrochloride (35.7 g, 0.166 mol) in DMF (100 mL) and DCM (200 mL). The reaction mixture was stirred for 4 h at ambient temperature then concentrated. EtOAc (500 mL) and water (500 mL) was added to the residue. The resulting two layers were separated and the aqueous phase was extracted with EtOAc (3×300 mL). The combined organic layers were washed with brine (3×500 mL), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (DCM/MeOH=100:3) to afford (S)-benzyl 2-(2-morpholinoacetamido)propanoate (21.1 g, 50% yield).

Workup

  1. concentrationthen concentrated
  2. additionEtOAc (500 mL) and water (500 mL) was added to the residue
  3. customThe resulting two layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc (3×300 mL)
  5. washThe combined organic layers were washed with brine (3×500 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography on silica gel (DCM/MeOH=100:3)

Sources & evidence

ORD record
ord-0ba05b0e9cb44a6b98f64f4e6600feba
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Linked notes

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