Cesium carbonate → Ethyl 2-(diphenylmethyleneamino)-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate

HRID 1506501Notes

Reaction equation

HRID 1506501 reaction equation
[C:1]1([C:7](=[N:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].[C:27]1([C:33]2[O:37][N:36]=[C:35]([C:38]3[O:42][N:41]=[C:40]4[C:43]5[C:48]([CH2:49][CH2:50][C:39]=34)=[CH:47][C:46]([CH:51]=[CH2:52])=[CH:45][CH:44]=5)[C:34]=2[C:53]([F:56])([F:55])[F:54])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CS(C)=O>[C:1]1([C:7](=[N:14][CH:15]([CH2:52][CH2:51][C:46]2[CH:47]=[C:48]3[C:43](=[CH:44][CH:45]=2)[C:40]2=[N:41][O:42][C:38]([C:35]4[C:34]([C:53]([F:55])([F:56])[F:54])=[C:33]([C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=5)[O:37][N:36]=4)=[C:39]2[CH2:50][CH2:49]3)[C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 319508Ethyl 2-(diphenylmethyleneamino)acetateHCID 671704243-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole

Product 1

HCID 86669931Ethyl 2-(diphenylmethyleneamino)-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoateYield 85%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of ethyl 2-(diphenylmethyleneamino)acetate (236 mg, 0.882 mmol), Cs2CO3 (144 mg, 0.441 mmol), 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole (Preparation 6A, 100 mg, 0.245 mmol), and anhydrous DMSO (0.6 mL) was purged with nitrogen for 5 min. and then sealed in a 1 dram vial. The mixture was stirred at 50° C. for 2 h. The mixture was cooled, diluted with water (15 mL) and extracted with ethyl acetate (3×5 mL). The combined ethyl acetate extracts were dried (sodium sulfate) and concentrated under reduced pressure. Flash chromatography purification (12 g silica gel column, 10→100% ethyl acetate in hexanes) afforded ethyl 2-(diphenylmethyleneamino)-4-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)butanoate (140 mg, 0.207 mmol, 85% yield) as a sticky liquid. The compound had an LC/MS M+1=676.2.

Workup

  1. customwas purged with nitrogen for 5 min.
  2. customsealed in a 1 dram vial
  3. temperatureThe mixture was cooled
  4. additiondiluted with water (15 mL)
  5. extractionextracted with ethyl acetate (3×5 mL)
  6. dry with materialThe combined ethyl acetate extracts were dried (sodium sulfate)
  7. concentrationconcentrated under reduced pressure
  8. customFlash chromatography purification (12 g silica gel column, 10→100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-afbc15cb3df9457fa91e8efc6051b7cc
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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