Water → HCID 86599885, compound

HRID 16174

Reaction equation

HRID 16174 reaction equation
Br[C:2]1[C:12]2[N:11]3[CH2:13][CH2:14][CH2:15][C@@H:16]([NH:17][C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[C@H:10]3[C:9]3[CH:24]=[CH:25][CH:26]=[CH:27][C:8]=3[O:7][C:6]=2[CH:5]=[C:4]([F:28])[CH:3]=1.[Cl-].[CH3:30][Zn+].O>C1COCC1.[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Fe+2].Cl[Pd]Cl>[F:22][C:19]([F:21])([F:20])[C:18]([NH:17][C@H:16]1[C@@H:10]2[N:11]([C:12]3[C:2]([CH3:30])=[CH:3][C:4]([F:28])=[CH:5][C:6]=3[O:7][C:8]3[CH:27]=[CH:26][CH:25]=[CH:24][C:9]=32)[CH2:13][CH2:14][CH2:15]1)=[O:23]

Participants

6

Reactant 3

HCID 962WaterHCID 86599886HCID 86599886, compoundHCID 178477797HCID 178477797, compound2×

Product 1

HCID 86599885HCID 86599885, compound

Reagents, catalysts & solvents 2

HCID 131728027Ferrocene palladium dichlorideCatalyst2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of trans-N-(6-bromo-8-fluoro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-2,2,2-trifluoroacetamide (300 mg, 0.65 mmol) in THF (7 mL) was added ferrocene PdCl2 (10 mg, 14 mmol) and the reaction mixture was stirred for 10 min. Methylzinc chloride (0.81 mL) was added dropwise whereafter the reaction mixture was heated to 60° C. After 3 h ferrocene PdCl2 (20 mg, 28 μmol) and methylzinc chloride (0.3 mL) were added and the reaction mixture was heated at 80° C. for another hour. Water was added at room temperature, and the reaction mixture was extracted with ether and water. The ether solution was washed with brine, dried (Na2SO4) and the volatiles were removed under reduced pressure. After purification by HPLC the title compound was obtained (108 mg, 39%). Data: 1H-NMR (400 MHz, CDCl3) 1.56-1.72 (m, 2H), 1.79-1.93 (m, 2H), 2.37 (s, 3H), 2.79-2.86 (m, 1H), 3.44-3.52 (td, J=12.0, J=3.0, 1H), 4.27-4.29 (d, J=2.5, 1H), 4.85-4.91 (m, 1H), 6.70-7.32 (6 ArH), 7.63-7.70 (br, 1H). (m/z)=395 (M+H)+.

Workup

  1. temperaturethe reaction mixture was heated at 80° C. for another hour
  2. extractionthe reaction mixture was extracted with ether and water
  3. washThe ether solution was washed with brine
  4. dry with materialdried (Na2SO4)
  5. customthe volatiles were removed under reduced pressure
  6. customAfter purification by HPLC the title compound
  7. customwas obtained (108 mg, 39%)

Sources & evidence

ORD record
ord-e17dd38f63e74f9e9e1613f0722afdd2
Source dataset
uspto-grants-2010_06
Patent number
US07737136B2

Linked notes

Loading…