Methanol → N-[2-(8-chloro-10,11-dihydrodibenz[b,f][1,4]oxazepin-10-yl)-2-oxoethyl]-3-[(2-furanylmethyl)thio]propanamide

HRID 248824Notes

Reaction equation

HRID 248824 reaction equation
C[Al](C)C.[O:5]1[CH:9]=[CH:8][CH:7]=[C:6]1[CH2:10][S:11][CH2:12][CH2:13][C:14]([O:16]C)=O.[NH2:18][CH2:19][C:20]([N:22]1[CH2:28][C:27]2[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=2[O:25][C:24]2[CH:33]=[CH:34][C:35]([Cl:37])=[CH:36][C:23]1=2)=[O:21].CO>C1(C)C=CC=CC=1>[Cl:37][C:35]1[CH:34]=[CH:33][C:24]2[O:25][C:26]3[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=3[CH2:28][N:22]([C:20](=[O:21])[CH2:19][NH:18][C:14](=[O:16])[CH2:13][CH2:12][S:11][CH2:10][C:6]3[O:5][CH:9]=[CH:8][CH:7]=3)[C:23]=2[CH:36]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 1066106110-(Aminoacetyl)-8-chloro-10,11-dihydrodibenz-[b,f][1,4]oxazepineHCID 15225386Methyl 3-(furfurylthio)propionateHCID 16682925Trimethylaluminum

Product 1

HCID 9933776N-[2-(8-chloro-10,11-dihydrodibenz[b,f][1,4]oxazepin-10-yl)-2-oxoethyl]-3-[(2-furanylmethyl)thio]propanamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Trimethylaluminum (2.0M in toluene; 4.6 mL) was added dropwise via syringe to a stirred solution of methyl 3-[(2-furanylmethyl)thio]propanoate (0.75 gram) and 10-(aminoacetyl)-8-chloro-10,11-dihydrodibenz[b,f][1,4]oxazepine (1.00 gram) in toluene (30 mL) at room temperature under nitrogen, and the reaction was stirred for 5 hours. Methanol (14 mL) was then added, and the reaction was stirred at room temperature overnight. The reaction was evaporated in vacuo, and the resulting orange residue was partitioned between chloroform (50 mL) and 1N NaOH (50 mL). The layers were separated and the aqueous layer was extracted with chloroform (50 mL). The combined chloroform extracts were washed with 1N NaOH (50 mL), 1N HCl (2×50 mL), and brine (50 mL), dried over MgSO4, and evaporated in vacuo. The crude product was purified by flash chromatography through silica gel 60 (350 mL) using 3:1 chloroform:ethyl acetate followed by recrystallization from cyclohexane/ethyl acetate. The yield of the title compound was 0.63 gram (40%) in the form of a tan solid. Analysis calculated for C23H21ClN2O4S: C, 60.46; H, 4.63; N, 6.13; Cl, 7.67; S, 7.02. Found: C, 60.16; H, 4.62; N, 6.05; Cl, 8.06; S, 7.02. DSC: 90°-95° C.

Workup

  1. stirringthe reaction was stirred at room temperature overnight
  2. customThe reaction was evaporated in vacuo
  3. customthe resulting orange residue was partitioned between chloroform (50 mL) and 1N NaOH (50 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with chloroform (50 mL)
  6. washThe combined chloroform extracts were washed with 1N NaOH (50 mL), 1N HCl (2×50 mL), and brine (50 mL)
  7. dry with materialdried over MgSO4
  8. customevaporated in vacuo
  9. customThe crude product was purified by flash chromatography through silica gel 60 (350 mL)
  10. customethyl acetate followed by recrystallization from cyclohexane/ethyl acetate
  11. custom90°-95° C.

Sources & evidence

ORD record
ord-45e8eade1d9b4d509bac4c104022c219
Source dataset
uspto-grants-1993_05
Patent number
US05212169

Reaction notes

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