Benzoyl isothiocyanate → HCID 90389345, compound

HRID 1526539Notes

Reaction equation

HRID 1526539 reaction equation
[NH2:1][C:2]([CH:14]1[CH2:16][CH:15]1[OH:17])([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:7]=1[CH3:13])[CH:3]([F:5])[F:4].[C:18]([N:26]=[C:27]=S)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC>C1COCC1.ClCCl.O>[F:5][CH:3]([F:4])[C:2]1([C:6]2[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:7]=2[CH3:13])[CH:14]2[CH:15]([CH2:16]2)[O:17][C:27]([NH:26][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[N:1]1

Participants

8

Reactant 4

HCID 68284Benzoyl isothiocyanateHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 90389354HCID 90389354, compound

Product 1

HCID 90389345HCID 90389345, compoundYield 86%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(1-amino-2,2-difluoro-1-(3-fluoro-2-methylphenyl)ethyl)cyclopropanol (0.61 g, 2.487 mmol) in dry THF (10 mL) under nitrogen was added benzoyl isothiocyanate (0.7 ml, 5.20 mmol) dropwise and the reaction was stirred for 30 min. Diisopropylethylamine (1.731 ml, 9.95 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.954 g, 4.97 mmol) were added and the reaction stirred at room temperature for 1 hour and then warmed to 60° C. for another 12 hr. The reaction mixture was diluted with dichloromethane and water. The phases were mixed, separated, and the organic was evaporated to dryness under reduced pressure. The crude residue was purified via silica gel flash chromatography eluting with 0-30% ethyl acetate in hexane afforded the title compound N-(5-(difluoromethyl)-5-(3-fluoro-2-methylphenyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-yl)benzamide (0.8 g, 2.137 mmol, 86% yield). LC/MS (ESI+) m/z=375.0 (M+H).

Workup

  1. stirringthe reaction stirred at room temperature for 1 hour
  2. additionThe phases were mixed
  3. customseparated
  4. customthe organic was evaporated to dryness under reduced pressure
  5. customThe crude residue was purified via silica gel flash chromatography
  6. washeluting with 0-30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-9cff6a7c004b460c86068f388668e942
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

Loading…