Toluene → HCID 58109153, compound

HRID 2037530Notes

Reaction equation

HRID 2037530 reaction equation
[CH2:1]([C@@:4]1([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].[F:27][C:28]([F:35])([F:34])[C:29]1[CH:33]=[CH:32][NH:31][N:30]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>CCOC(C)=O.[Cu]I>[CH2:1]([C@@:4]1([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([N:31]3[CH:32]=[CH:33][C:29]([C:28]([F:35])([F:34])[F:27])=[N:30]3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 18070343-(Trifluoromethyl)pyrazoleHCID 53473487(R)-6-allyl-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one

Product 1

HCID 58109153HCID 58109153, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

(R)-6-Allyl-3-((S)-1-(4-bromophenyl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (20 mg, 0.048 mmol), 3-(trifluoromethyl)-1H-pyrazole (20 mg, 3 equiv.), CuI (1.4 mg, 15% mol), (1R,2R)-(−)-1,2-transcyclohexanediamine (2 mg, 30% mol), K3PO4 (20 mg, 2 equiv.) were mixed with dry toluene (2 mL) and heated in Microwave Oven for 1 h at 130° C. LC-MS found product peak. The mixture was diluted with EtOAc (8 mL), washed by water (2 mL), brine (3 mL) and dried over Na2SO4. After filtration and concentration, the residue was purified chromatography on a 4-g silica gel cartridge eluted with a gradient from 5 to 55% EtOAc in gexanes to afford (R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-(3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)ethyl)-1,3-oxazinan-2-one (9.7 mg, 43%) product. LC-MS Method 1 tR=2.05, min, m/z=474; 1H NMR (CDCl3) 7.86 (s, 1H), 7.43 (d, 2H), 7.26 (t, 2H), 7.01 (dd, 2H), 6.69 (d, 1H), 5.76-5.64 (m, 2H), 5.05 (dd, 2H), 2.95 (m, 1H), 2.65-2.51 (m, 2H), 1.54 (d, 3H).

Workup

  1. washwashed by water (2 mL), brine (3 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationAfter filtration and concentration
  4. customthe residue was purified chromatography on a 4-g silica gel cartridge
  5. washeluted with a gradient from 5 to 55% EtOAc in gexanes

Sources & evidence

ORD record
ord-9ff9b2574a1d4536a24cb08e4f010fd6
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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