1,2-Dichloroethane → HCID 15885802, compound

HRID 1840866Notes

Reaction equation

HRID 1840866 reaction equation
[CH:1]1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[C:14]([O:18][C:19](=[O:23])[C@H:20]([CH3:22])[NH2:21])([CH3:17])([CH3:16])[CH3:15].[NH2:24][C:25]1[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[C:26]=1[C:27]([OH:29])=[O:28].C(N(CC)CC)C.C(Cl)CCl>N1C=CC=CC=1.CCOC(C)=O>[CH3:34][C:30]1[C:26]2[C:27](=[O:29])[O:28][C:1]([NH:21][C@H:20]([C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:23])[CH3:22])=[N:24][C:25]=2[CH:33]=[CH:32][CH:31]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 1512106-Methylanthranilic acidHCID 11275390tert-Butyl alaninate hydrochloride

Product 1

HCID 15885802HCID 15885802, compoundYield 13%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To an ice cooled suspension of CDI (0.53 g, 3.27 mmol) in 5 mL of pyridine was added L-alanine t-butyl ester hydrochloride (0.57 g, 3.13 mmol). After stirring at 0° C. for 30 minutes, 2-amino-6-methylbenzoic acid (0.43 g, 2.85 mmol) was added. The ice bath was removed and the reaction was stirred at 65° C. for 2 hours. The reaction mixture was diluted with EtOAc and washed with 1N HCl, dried (MgSO4), filtered and evaporated under reduced pressure. The crude product (0.30 g) was dissolved in 5 mL of CH2Cl2. Triethylamine (0.15 g, 1.47 mmol) and EDC (0.28 g, 1.47 mmol) were added sequentially. After stirring at room temperature for 2 hours the reaction mixture was diluted with EtOAc and washed with 1N HCl, dried (MgSO4), filtered and evaporated under reduced pressure. Silica gel chromatography of the residue (1:1 EtOAc/hexane) afforded 113 mg of N-(5-methyl-4-oxo-4H-3,1-benzoxazin-2-yl)-L-alanine, t-butyl ester: Anal. Calc'd. for C16H20N2O4: C, 63.14; H, 6.62; N, 9.21. Found: C, 62.90; H, 6.97; N, 9.11. 1H-NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 1.50 (d, J=7 Hz, 3H), 2.70 (s, 3H), 4.48 (pent, J=7 Hz, 1H), 5.68 (br. s, 1H, exchangeable), 6.95 (d, J=8 Hz, 1H), 6.99 (d, J=8 Hz, 1H), 7.45 (t, J=8 Hz, 1H).

Workup

  1. customThe ice bath was removed
  2. stirringthe reaction was stirred at 65° C. for 2 hours
  3. additionThe reaction mixture was diluted with EtOAc
  4. washwashed with 1N HCl
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. dissolutionThe crude product (0.30 g) was dissolved in 5 mL of CH2Cl2
  9. stirringAfter stirring at room temperature for 2 hours the reaction mixture
  10. washwashed with 1N HCl
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-79125dde647a42b0b7fcf6b0cf4b4b4a
Source dataset
uspto-grants-2004_01
Patent number
US06683077B2

Reaction notes

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