Tetrahydrofuran → Methyl 2,3-dimethyl-2-[(1-oxo-2,3-benzoxazin-4-yl)amino]butyrate

HRID 973362Notes

Reaction equation

HRID 973362 reaction equation
[NH2:1][C:2]([CH3:10])([CH:7]([CH3:9])[CH3:8])[C:3]([O:5][CH3:6])=[O:4].C([N:13]([CH2:16][CH3:17])CC)C.O1CCCC1.ClC([C:26]1[CH:41]=[CH:40][CH:39]=C[C:27]=1[C:28]([O:30]CC1C=CC=CC=1)=[O:29])=O>C(Cl)Cl>[CH3:10][C:2]([NH:1][C:16]1[C:17]2[CH:39]=[CH:40][CH:41]=[CH:26][C:27]=2[C:28](=[O:29])[O:30][N:13]=1)([CH:7]([CH3:9])[CH3:8])[C:3]([O:5][CH3:6])=[O:4]

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 13018902Methyl 2-amino-2,3-dimethylbutanoateHCID 22127333Benzyl o-(chloroformyl)benzoate

Product 1

HCID 15029344Methyl 2,3-dimethyl-2-[(1-oxo-2,3-benzoxazin-4-yl)amino]butyrateYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl 2-amino-2,3-dimethylbutyrate (2.76 g, 0.019 mol), and triethylamine (1.97 g, 0.0195 mol) and tetrahydrofuran is added dropwise to a 5° C. mixture of benzyl o-(chloroformyl)benzoate, o-oxime (6.0 g, 0.02 mol) (which is prepared following the procedure in examples 1 and 2 ) and tetrahydrofuran under a nitrogen stream. The reaction mixture is stirred at room temperature for 21 hours, filtered to remove solids and the filtrate is concentrated in vacuo to give a yellow oil. The oil is dissolved into methylene chloride. The methylene chloride solution is washed sequentially with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a yellow oil. Crystallization of the oil from a benzene/hexanes/methylene chloride solution yields a white solid. The solid i chromatographed using neutral alumina and 4% ethyl acetate in methylene chloride as eluent to give the title compound as a white solid (2.41 g, 40%), mp 132°-134°, identified by IR and NMR spectral analyses.

Workup

  1. customis prepared
  2. filtrationfiltered
  3. customto remove solids
  4. concentrationthe filtrate is concentrated in vacuo
  5. customto give a yellow oil
  6. washThe methylene chloride solution is washed sequentially with water and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give a yellow oil
  10. customCrystallization of the oil from a benzene/hexanes/methylene chloride solution
  11. customyields a white solid
  12. customThe solid i chromatographed

Sources & evidence

ORD record
ord-13983af3d1754c3896444d5d60d7e743
Source dataset
uspto-grants-1991_11
Patent number
US05062881

Reaction notes

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