Diisopropylethylamine → 3,5-Dichlorobenzyl 2-(2-(N-methyl-2-oxo-2,3-dihydrooxazole-5-carboxamido)ethyl)morpholine-4-carboxylate

HRID 1480386Notes

Reaction equation

HRID 1480386 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][CH:5]1[O:10][CH2:9][CH2:8][N:7]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[C:19]([Cl:21])[CH:18]=[C:17]([Cl:22])[CH:16]=2)=[O:12])[CH2:6]1.[O:23]=[C:24]1[NH:28][CH:27]=[C:26]([C:29](O)=[O:30])[O:25]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:1][N:2]([CH2:3][CH2:4][CH:5]1[O:10][CH2:9][CH2:8][N:7]([C:11]([O:13][CH2:14][C:15]2[CH:16]=[C:17]([Cl:22])[CH:18]=[C:19]([Cl:21])[CH:20]=2)=[O:12])[CH2:6]1)[C:29]([C:26]1[O:25][C:24](=[O:23])[NH:28][CH:27]=1)=[O:30]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 539814232-Hydroxy-1,3-oxazole-5-carboxylic acidHCID 867226373,5-Dichlorobenzyl 2-(2-(methylamino)ethyl)morpholine-4-carboxylate

Product 1

HCID 762863523,5-Dichlorobenzyl 2-(2-(N-methyl-2-oxo-2,3-dihydrooxazole-5-carboxamido)ethyl)morpholine-4-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture comprising of 3,5-dichlorobenzyl 2-(2-(methylamino)ethyl)morpholine-4-carboxylate (step 2)(169 mg, 0.487 mmol), 2-oxo-2,3-dihydrooxazole-5-carboxylic acid ((Example 21, step 1)) (161 mg, 0.487 mmol), T3P® (50% in DMF) (426 μl, 0.730 mmol) and Huenig's base (425 μl, 2.433 mmol) in DMF (1622 μl) was stirred at room temperature for 20 hours. The resulting mixture was diluted with EtOAc and washed with water. The organic portion was dried with MgSO4, filtered and concentrated under reduced pressure. The crude material was dry loaded with silica onto an ISCO 4 g column eluting with 0-100% EtOAc (1% acetic acid) in iso-hexane. The product fractions were concentrated under reduced pressure to afford the title compound;

Workup

  1. washwashed with water
  2. dry with materialThe organic portion was dried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. dry with materialThe crude material was dry
  6. washeluting with 0-100% EtOAc (1% acetic acid) in iso-hexane
  7. concentrationThe product fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-e0dc003004fe4d28ab49b198ea48458d
Source dataset
uspto-grants-2016_08
Patent number
US09409895B2

Reaction notes

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