Nitrogen → HCID 71475693, compound

HRID 2400261Notes

Reaction equation

HRID 2400261 reaction equation
[F:1][C:2]([F:31])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]([C:14]2([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])[CH2:16][O:15]2)([F:13])[F:12])=[N:9][CH:10]=1.[NH:32]1[CH:36]=[N:35][N:34]=[N:33]1.C([O-])([O-])=O.[K+].[K+].N#N.[NH4+].[Cl-]>CS(C)=O.C(Cl)Cl>[F:31][C:2]([F:1])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]([F:13])([F:12])[C:14]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[F:24])([OH:15])[CH2:16][N:32]2[CH:36]=[N:35][N:34]=[N:33]2)=[N:9][CH:10]=1

Participants

8

Reactant 5

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 86675116HCID 86675116, compoundHCID 178418441HCID 178418441, compound

Product 1

HCID 71475693HCID 71475693, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a magnetically stirred mixture of 5-(2,2-difluoro-2-phenylethoxy)-2-((2-(2,4-difluorophenyl)oxiran-2-yl)difluoromethyl)pyridine (81 mg, 0.184 mmol, compound X), and 1H-tetrazole (19.37 mg, 0.277 mmol) in dry DMSO (1229 μl) was added K2CO3 (28.0 mg, 0.203 mmol) in a 20 mL vial under N2 atmosphere. The reaction mixture was stirred at 60° C. overnight. The reaction was cooled to rt, diluted with CH2Cl2 and poured into a separatory funnel containing sat. aq. NH4Cl. The organic layer was washed and then the aqueous layer was back extracted twice with CH2Cl2. The combined organic layers were then washed three times with water and dried by passing through a phase separator. Volatiles were removed by rotary evaporation and the resulting residue was loaded onto a pad of SiO2 and purified (ISCO, 12 g SiO2, 20-60% ethyl acetate to hexanes over 7 min followed by 7 min at 60%) to afford the title compound 119. Yield=56 mg (59.6%) of a light yellow viscous oil. 1H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H), 8.21 (d, J=2.8 Hz, 1H), 7.57-7.45 (m, 6H), 7.41 (s, 1H), 7.33-7.24 (m, 2H), 6.80-6.70 (m, 1H), 6.70-6.62 (m, 1H), 5.58 (d, J=14.3 Hz, 1H), 5.07 (d, J=15.1 Hz, 1H), 4.42 (t, J=11.9 Hz, 2H). 1H decoupled-19F NMR (376 MHz, CDCl3) δ −102.97 (dd, J=261.4, 15.2 Hz, 1F), −103.88 (ddd, J=43.5, 14.9, 9.8 Hz, 1F), −104.07 (s, 2F), −108.15 (d, J=9.7 Hz, 1F), −110.87 (dd, J=261.4, 43.2 Hz, 1F). MS(ESI): m/z calcd for C23H17F6N5O2: 509.404; found: 510.2 (M+H)+, 508.6 (M−H)−.

Workup

  1. temperatureThe reaction was cooled to rt
  2. additionpoured into a separatory funnel
  3. washThe organic layer was washed
  4. extractionthe aqueous layer was back extracted twice with CH2Cl2
  5. washThe combined organic layers were then washed three times with water
  6. customdried
  7. customVolatiles were removed by rotary evaporation
  8. custompurified (ISCO, 12 g SiO2, 20-60% ethyl acetate to hexanes over 7 min followed by 7 min at 60%)

Sources & evidence

ORD record
ord-70967881e94f44c8b7abe37ef40b9a7d
Source dataset
uspto-grants-2014_08
Patent number
US08796001B2

Reaction notes

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