Borane;tetrahydrofuran → HCID 57748785, compound

HRID 1670616Notes

Reaction equation

HRID 1670616 reaction equation
B.C1COCC1.[Br:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C@@H:15]2[CH2:23][N:22]3[C@H:17]([CH2:18][O:19][CH2:20][C:21]3=O)[CH2:16]2)=[C:10]([N+:25]([O-:27])=[O:26])[CH:9]=1>O1CCCC1>[Br:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C@@H:15]2[CH2:23][N:22]3[C@H:17]([CH2:18][O:19][CH2:20][CH2:21]3)[CH2:16]2)=[C:10]([N+:25]([O-:27])=[O:26])[CH:9]=1

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 57748794HCID 57748794, compound

Product 1

HCID 57748785HCID 57748785, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Add BH3.THF (1.0 M in tetrahydrofuran, 0.056 mol, 56 mL) drop wise to a solution of (7S,8aS)-7-(4-bromo-2-nitro-phenylamino)-tetrahydro-pyrrolo[2,1-c][1,4]oxazin-4-one (0.028 mol, 10 g) in tetrahydrofuran (150 mL) at 0 to −5° C. under nitrogen. After complete addition, reflux the reaction mixture for 3 h. Cool the reaction mixture to 0° C., quench with 1 N hydrochloric acid, and then add 1 N aqueous sodium hydroxide solution. Remove tetrahydrofuran under reduced pressure and extract the aqueous layer with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate. Dissolve the residue in methanol (160 mL), add 4 N hydrogen chloride in dioxane (160 mL) and heat the reaction mixture for 4 h at 80° C. Cool to room temperature and adjust the pH between 10-12 by adding 4 N aqueous sodium hydroxide solution. Remove the methanol under reduced pressure and extract the aqueous layer with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate to give the title compound as a crystalline, yellow solid (8.0 g, 83%). 1H NMR (400 MHz, CDCl3) δ 1.32-1.38 (m, 1H), 2.19-2.22 (m, 1H), 2.34 (dt, 1H), 2.42-2.47 (m, 1H), 2.54-2.58 (m, 1H), 2.92 (d, 1H), 3.07 (d, 1H), 3.34 (t, 1H), 3.61 (dt, 1H), 3.85 (dd, 1H), 3.97 (dd, 1H), 4.01-4.07 (m, 1H), 6.67 (d, 1H), 7.48 (dd, 1H), 8.17 (d, 1H), 8.35 (d, 1H).

Workup

  1. additionAfter complete addition
  2. temperaturereflux the reaction mixture for 3 h
  3. customquench with 1 N hydrochloric acid
  4. additionadd 1 N aqueous sodium hydroxide solution
  5. extractionRemove tetrahydrofuran under reduced pressure and extract the aqueous layer with dichloromethane
  6. dry with materialDry the organic layer over anhydrous sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate
  9. dissolutionDissolve the residue in methanol (160 mL)
  10. additionadd 4 N hydrogen chloride in dioxane (160 mL)
  11. temperatureheat the reaction mixture for 4 h at 80° C
  12. temperatureCool to room temperature
  13. additionby adding 4 N aqueous sodium hydroxide solution
  14. customRemove the methanol under reduced pressure
  15. extractionextract the aqueous layer with dichloromethane
  16. dry with materialDry the organic layer over anhydrous sodium sulfate
  17. filtrationfilter
  18. concentrationconcentrate

Sources & evidence

ORD record
ord-1b4d3210be8f4ae68e15a2f1b266e406
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

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