Reaktion #496549

Reaktionsgleichung

N2

glycine

B1

6-Chloro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione

→

pure product

Ausbeute 44.0%

7-Chloro-1-methyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

Ausbeute 44.0%

Lösungsmittel

AcOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeReaction flask
2. 2
   SonstigeSolvent was evaporated under suction
3. 3
   Temperaturwith heating (50-60° C.)
4. 4
   workup.ADDITIONTo the thick syrupy crude product was added 1 L of EtOAc
5. 5
   workup.ADDITIONfollowed by the slow addition of aqueous NaHCO3 (saturated)
6. 6
   workup.ADDITIONThen 10 mL of 2 M NaOH was added
7. 7
   SonstigeThe mixture gave a solid along with organic and aqueous layers
8. 8
   FiltrationThe solid was filtered
9. 9
   Sonstigeto give product
10. 10
    workup.ADDITIONcontaining some impurity
11. 11
    SonstigeThe solid was partitioned between 400 mL dichloromethane (DCM) and 200 mL NaHCO3
12. 12
    Filtrationfiltered
13. 13
    Sonstigeto remove an insoluble impurity
14. 14
    SonstigeThe DCM layer was separated
15. 15
    Waschenwashed with 3% NaHCO3
16. 16
    TrocknenThe DCM layer was dried (MgSO4)
17. 17
    Filtrationfiltered
18. 18
    Einengenconcentrated

Vorschrift

In a 2 L RBF equipped with mechanical stir, condenser and N2 inlet, glycine (38 g, 0.506 mol) was added to crude B1 (107 g, 0.506 mol) followed by the addition of AcOH (500 mL). Reaction flask was heated in a 130° C. oil bath for 7 h. Solvent was evaporated under suction with heating (50-60° C.). To the thick syrupy crude product was added 1 L of EtOAc followed by the slow addition of aqueous NaHCO3 (saturated) to adjust the pH to −7. Then 10 mL of 2 M NaOH was added to adjust the pH to ˜9-10. The mixture gave a solid along with organic and aqueous layers. The solid was filtered to give product containing some impurity. The solid was partitioned between 400 mL dichloromethane (DCM) and 200 mL NaHCO3, and the resultant slurry was stirred for 20 min, then filtered to remove an insoluble impurity. The DCM layer was separated and washed with 3% NaHCO3 and then brine (200 mL). The DCM layer was dried (MgSO4), filtered and concentrated to give 50 g of pure product. EtOAc layer was concentrated to give 67 g of solid product with some impurity. The aqueous layer was extracted with EtOAc (2×400 mL). Combined organics were dried over Na2SO4, filtered and concentrated to give an additional 6.7 g of crude product. Total of 123.4 g of product was obtained, 50 g of which was very clean (yield ˜quantitative). 1H NMR (300 MHz, CDCl3) δ 3.2 (s, 3H), 3.5 (m, 1H), 3.8 (m, 1H), 7.35 (d, 1H), 7.6 (m, 2H), 8.8 (t, 1H).

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