Hydrochloric Acid → trans-N-(6,7-Dichloro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)acetamide

HRID 16169Notes

Reaction equation

HRID 16169 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][C:5]2[O:6][C:7]3[CH:22]=[CH:21][CH:20]=[CH:19][C:8]=3[C@@H:9]3[C@H:14]([NH:15][C:16](=[O:18])[CH3:17])[CH2:13][CH2:12][CH2:11][N:10]3[C:4]=2[CH:3]=1.[Cl:25]N1C(=O)CCC1=O.Cl>CC(C)=O>[Cl:25][C:3]1[C:4]2[N:10]3[CH2:11][CH2:12][CH2:13][C@@H:14]([NH:15][C:16](=[O:18])[CH3:17])[C@H:9]3[C:8]3[CH:19]=[CH:20][CH:21]=[CH:22][C:7]=3[O:6][C:5]=2[CH:23]=[CH:24][C:2]=1[Cl:1]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 31398Chlorosuccinimide2×HCID 86599858HCID 86599858, compound

Product 1

HCID 86599877trans-N-(6,7-Dichloro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)acetamideYield 36.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of trans-N-(7-chloro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]-pyrido[1,2-d][1,4]oxazepin1-yl)acetamide (Structure 12 of Scheme II, where R1=H, R2=H, R3=Cl, R4=R5=H, R15=CH3, X=O) (0.63 g, 1.84 mmol) in acetone (15 mL) were added N-chlorosuccinimide (246 mg, 1.84 mmol) and 6N (aq) HCl (3.1 mL). The resulting suspension was stirred at room temperature for 20 h. A second amount of N-chlorosuccinimide (246 mg, 1.84 mmol) was added and subsequently the reaction mixture was stirred at room temperature for 4 h. The reaction mixture was extracted with ethyl acetate (3×), washed with sat. (aq) NaHCO3 (3×), 10% (aq) NaCl (2×) and dried (Na2SO4). The solvents were removed under reduced pressure. The solid was purified by column chromatography (silicagel, toluene/ethanol=9/1). Subsequent purification by HPLC resulted in the title compound (137 mg, 36.4%). Data: 1H-NMR (400 MHz, CDCl3) 1.55 (m, 1H), 1.82 (m, 2H), 1.94-2.20 (m, 1H), 2.10 (s, 3H), 2.92 (m, 1H), 3.11 (td, J=12.6, 4.2, 1H), 4.39 (d, J=1.9, 1H), 4.86 (m, 1H), 7.02-7.36 (m, 6 ArH).

Workup

  1. stirringsubsequently the reaction mixture was stirred at room temperature for 4 h
  2. extractionThe reaction mixture was extracted with ethyl acetate (3×)
  3. washwashed with sat. (aq) NaHCO3 (3×), 10% (aq) NaCl (2×)
  4. dry with materialdried (Na2SO4)
  5. customThe solvents were removed under reduced pressure
  6. customThe solid was purified by column chromatography (silicagel, toluene/ethanol=9/1)
  7. customSubsequent purification by HPLC

Sources & evidence

ORD record
ord-c848d06b4f0a491d9a864b04a771e317
Source dataset
uspto-grants-2010_06
Patent number
US07737136B2

Reaction notes

Loading…