Hydrochloric Acid → HCID 90082651, compound

HRID 1771967Notes

Reaction equation

HRID 1771967 reaction equation
B(Cl)(Cl)Cl.[O:5]1[CH2:10][CH2:9][NH:8][C:7]2[CH:11]=[CH:12][CH:13]=[CH:14][C:6]1=2.[Cl-].[Al+3].[Cl-].[Cl-].[CH3:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[C:23]#N.Cl.[OH-:29].[Na+]>C1(C)C=CC=CC=1>[O:5]1[CH2:10][CH2:9][NH:8][C:7]2[C:11]([C:23]([C:22]3[CH:21]=[C:20]([CH3:19])[CH:27]=[CH:26][CH:25]=3)=[O:29])=[CH:12][CH:13]=[CH:14][C:6]1=2

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 121043-TolunitrileHCID 14798Sodium HydroxideHCID 25135Boron TrichlorideHCID 5850963,4-Dihydro-2H-1,4-benzoxazineHCID 6451240Aluminum(III) Chloride

Product 1

HCID 90082651HCID 90082651, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

A dried 200 mL round bottom was charged with boron trichloride (1.0 M PhMe) (4.67 mL, 4.67 mmol) and cooled to 0° C. for 15 min. Next, 3,4-dihydro-2H-benzo[b][1,4]oxazine (574 mg, 4.25 mmol) in toluene (Volume: 9.4 mL) was added dropwise over about 5 min, and then the solution was stirred for 10 minutes. Aluminum chloride (623 mg, 4.67 mmol) was added and the solution was stirred for 5 minutes. Then, 3-methylbenzonitrile (0.605 mL, 5.10 mmol) was added. The reaction mixture was stirred at 0° C., for about 1 h, then allowed to warm to room temperature and heated to reflux for 8 h. HCl (1.5 M) (28.3 mL, 42.5 mmol) was added, and the reaction mixture was heated to reflux for 2 h. The reaction mixture was cooled to room temperature, basified to pH 9 with 1 M NaOH, and extracted three times with CH2Cl2. The organic layers were dried with MgSO4 and evaporated. The residue was purified via ISCO (40 g column; hex/EtOAc; 2 min, 0%, 27 min, 40%, 30 min 40%;) to afford (3,4-dihydro-2H-benzo[b][1,4]oxazin-5-yl)(m-tolyl)methanone, Intermediate C-1A (0.73 g, 2.9 mmol, 68%)1H NMR (400 MHz, chloroform-d) δ 8.31 (br. s., 1H), 7.47-7.39 (m, 2H), 7.37-7.33 (m, 2H), 7.12 (dd, J=8.1, 1.5 Hz, 1H), 6.99-6.88 (m, 1H), 6.48 (t, J=7.9 Hz, 1H), 4.29 (t, J=4.5 Hz, 2H), 3.63 (td, J=4.6, 2.8 Hz, 2H), 2.43 (s, 3H).

Workup

  1. stirringthe solution was stirred for 5 minutes
  2. stirringThe reaction mixture was stirred at 0° C., for about 1 h
  3. temperatureto warm to room temperature
  4. temperatureheated
  5. temperatureto reflux for 8 h
  6. temperaturethe reaction mixture was heated
  7. temperatureto reflux for 2 h
  8. temperatureThe reaction mixture was cooled to room temperature
  9. extractionextracted three times with CH2Cl2
  10. dry with materialThe organic layers were dried with MgSO4
  11. customevaporated
  12. customThe residue was purified via ISCO (40 g column; hex/EtOAc; 2 min, 0%, 27 min, 40%, 30 min 40%;)

Sources & evidence

ORD record
ord-aa99626538514692ae587b9ce38751cf
Source dataset
uspto-grants-2016_02
Patent number
US09249157B2

Reaction notes

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