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

HRID 1480383Notes

Reaction equation

HRID 1480383 reaction equation
[NH2:1][CH2:2][CH2:3][CH:4]1[O:9][CH2:8][CH2:7][N:6]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[C:16]([Cl:21])[CH:15]=2)=[O:11])[CH2:5]1.[O:22]=[C:23]1[NH:27][CH:26]=[C:25]([C:28](O)=[O:29])[O:24]1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>CN(C=O)C>[O:22]=[C:23]1[NH:27][CH:26]=[C:25]([C:28]([NH:1][CH2:2][CH2:3][CH:4]2[O:9][CH2:8][CH2:7][N:6]([C:10]([O:12][CH2:13][C:14]3[CH:19]=[C:18]([Cl:20])[CH:17]=[C:16]([Cl:21])[CH:15]=3)=[O:11])[CH2:5]2)=[O:29])[O:24]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 539814232-Hydroxy-1,3-oxazole-5-carboxylic acid2×HCID 867226353,5-Dichlorobenzyl 2-(2-aminoethyl)morpholine-4-carboxylate

Product 1

HCID 762861973,5-Dichlorobenzyl 2-(2-(2-oxo-2,3-dihydrooxazole-5-carboxamido)ethyl)morpholine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture comprising of 3,5-dichlorobenzyl 2-(2-aminoethyl)morpholine-4-carboxylate (Example 11, step 2) (178 mg, 0.534 mmol), 2-oxo-2,3-dihydrooxazole-5-carboxylic acid (Example 21, step 1) (68.9 mg, 0.534 mmol), T3P® (50% in DMF) (510 mg, 0.801 mmol), Huenig's base (466 μl, 2.67 mmol) in DMF (1781 μl) was stirred at room temperature. Another 1 equivalent of 2-oxo-2,3-dihydrooxazole-5-carboxylic acid was added and the reaction mixture was left stirring at room temperature overnight. The resulting reaction mixture was concentrated under reduced pressure and the crude product was diluted with EtOAc. The organic portion was dried with MgSO4, filtered and concentrated under reduced pressure. The crude material was dried loaded using 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. waitthe reaction mixture was left
  2. customThe resulting reaction mixture
  3. concentrationwas concentrated under reduced pressure
  4. additionthe crude product was diluted with EtOAc
  5. dry with materialThe organic portion was dried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dry with materialThe crude material was dried
  9. washeluting with 0-100% EtOAc (1% acetic acid) in iso-hexane
  10. concentrationThe product fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-fa4a7d074d16437485ec2946b23613fd
Source dataset
uspto-grants-2016_08
Patent number
US09409895B2

Reaction notes

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