Tetrahydrothiophene → 5-Phenyl-1-(piperidin-4-yl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one

HRID 1379992Notes

Reaction equation

C(OC([N:6]1[CH2:11][CH2:10][CH:9]([N:12]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[C:16]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[N:15][CH2:14][C:13]2=[O:29])[CH2:8][CH2:7]1)=O)C.S1CCCC1.CS(O)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CCOCC>[C:23]1([C:16]2[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:12]([CH:9]3[CH2:8][CH2:7][NH:6][CH2:11][CH2:10]3)[C:13](=[O:29])[CH2:14][N:15]=2)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 1 g (2.6 mmol) of 12 in 1.1 ml (2.6×5 mmol) of tetrahydrothiophene is added 2 ml of methanesulfonic acid, and the mixture is heated at 110° C. (bath temperature) for 50 minutes. The reaction mixture is poured into ice water and shaken with ether. The aqueous layer is besified with aqueous potassium carbonate and extracted with methylene chloride. The methylene chloride layer is concentrated, and the residue is dissolved in 1 ml of methanol and mixed with 0.27 ml of 48% hydrobromic acid. The resultant crystals are recrystallized from methylene chloride-methanol to give 881 mg of 13 as crystals melting at 281°-283° C. (dec.). The yield is 86%.

Workup

extractionextracted with methylene chloride
concentrationThe methylene chloride layer is concentrated
dissolutionthe residue is dissolved in 1 ml of methanol
additionmixed with 0.27 ml of 48% hydrobromic acid
customThe resultant crystals are recrystallized from methylene chloride-methanol

Sources & evidence

ORD record: ord-ccad5f785af1408d9fef6eaa6640aa97
Source dataset: uspto-grants-1986_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04579685

Reaction notes

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