Potassium Carbonate → tert-butyl [(5-chloro-2-fluoro-4-{2-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenoxy}phenyl)sulfonyl]1,3-thiazol-4-ylcarbamate

HRID 46390Notes

Reaction equation

HRID 46390 reaction equation
[N+:1]([C:4]1[C:8]([C:9]2[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=2[OH:19])=[CH:7][N:6]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[N:5]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].[Cl:32][C:33]1[C:34](F)=[CH:35][C:36]([F:55])=[C:37]([S:39]([N:42]([C:50]2[N:51]=[CH:52][S:53][CH:54]=2)[C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])(=[O:41])=[O:40])[CH:38]=1>CS(C)=O.C(OCC)(=O)C.ClC1C(F)=CC(F)=C(S(N(C2N=CSC=2)C(=O)OC(C)(C)C)(=O)=O)C=1>[Cl:32][C:33]1[C:34]([O:19][C:10]2[CH:11]=[CH:12][C:13]([C:15]([F:17])([F:18])[F:16])=[CH:14][C:9]=2[C:8]2[C:4]([N+:1]([O-:3])=[O:2])=[N:5][N:6]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][O:21]3)[CH:7]=2)=[CH:35][C:36]([F:55])=[C:37]([S:39]([N:42]([C:50]2[N:51]=[CH:52][S:53][CH:54]=2)[C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])(=[O:41])=[O:40])[CH:38]=1

Participants

7

Reactant 3

HCID 11430Potassium Carbonate2×HCID 59436581Tert-butyl (5-chloro-2,4-difluorophenyl)sulfonyl(thiazol-4-yl)carbamateHCID 669055812-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenol

Product 1

HCID 66905740tert-butyl [(5-chloro-2-fluoro-4-{2-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenoxy}phenyl)sulfonyl]1,3-thiazol-4-ylcarbamateYield 70%

Reagents, catalysts & solvents 3

HCID 59436581Tert-butyl (5-chloro-2,4-difluorophenyl)sulfonyl(thiazol-4-yl)carbamateCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 2-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenol (Preparation 868, 28.73 g, 80.41 mmol) in dimethyl sulfoxide (175 mL) was added potassium carbonate (22.3 g, 161 mmol). After stirring for 10 minutes, tert-butyl [(5-chloro-2,4-difluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamate (Preparation 453, 33.02 g, 80.37 mmol) was added. After stirring for 14 hours at room temperature, additional potassium carbonate (4.7 g, 34 mmol) and tert-butyl [(5-chloro-2,4-difluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamate (1.25 g, 3.0 mmol) were added and the reaction mixture heated at 45° C. for 7 hours. The mixture was allowed to cool, diluted with ethyl acetate, and washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. Purification by manual flash column chromatography using 25% ethyl acetate/hexanes and an 8×46 cm column provided product as a yellow oil (40 g, 70%).

Workup

  1. stirringAfter stirring for 14 hours at room temperature
  2. temperatureto cool
  3. washwashed with water and brine
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by manual flash column chromatography

Sources & evidence

ORD record
ord-a9c4ec1b4a7a4cf29fe919a2076196b1
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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