Hydrochloric Acid → HCID 90418583, compound

HRID 2177311Notes

Reaction equation

HRID 2177311 reaction equation
Br[C:2]1[S:6][N:5]=[C:4]([C:7]([F:10])([F:9])[F:8])[C:3]=1[CH2:11][O:12][C:13]1[C:18]([F:19])=[CH:17][C:16]([CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[CH:15][C:14]=1[F:26].[Cl:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][C:29]=1[F:37].[O-]P([O-])([O-])=O.[K+].[K+].[K+].Cl>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([C:2]2[S:6][N:5]=[C:4]([C:7]([F:10])([F:9])[F:8])[C:3]=2[CH2:11][O:12][C:13]2[C:18]([F:19])=[CH:17][C:16]([CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[CH:15][C:14]=2[F:26])=[CH:30][C:29]=1[F:37]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 27786564-Chloro-3-fluorophenylboronic AcidHCID 90418267HCID 90418267, compound

Product 1

HCID 90418583HCID 90418583, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Into a 25-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed methyl 3-(4-[[5-bromo-3-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl)propanoate (70 mg, 0.15 mmol, 1.00 equiv), (4-chloro-3-fluorophenyl)boronic acid (32 mg, 0.18 mmol, 1.20 equiv), K3PO4 (161 mg, 0.76 mmol, 5.00 equiv), Pd(PPh3)4 (17.3 mg, 0.01 mmol, 0.10 equiv), dioxane (1.5 mL). The resulting solution was stirred for 2 h at 90° C. in an oil bath. The reaction progress was monitored by TLC (ethyl acetate/petroleum ether=1:5). The pH value of the solution was adjusted to 6 with hydrogen chloride (2 mol/L). The resulting mixture was washed with 1×2 mL of H2O. The resulting solution was extracted with 3×2 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. The residue was applied onto a TLC-Plate with ethyl acetate/petroleum ether (1:6). This resulted in 80 mg (98%) of methyl 3-(4-[[5-(4-chloro-3-fluorophenyl)-3-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl)propanoate as yellow oil.

Workup

  1. customInto a 25-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. washThe resulting mixture was washed with 1×2 mL of H2O
  4. extractionThe resulting solution was extracted with 3×2 mL of ethyl acetate
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe solids were filtered out
  7. concentrationThe resulting mixture was concentrated under vacuum
  8. customThis resulted in 80 mg (98%) of methyl 3-(4-[[5-(4-chloro-3-fluorophenyl)-3-(trifluoromethyl)-1,2-thiazol-4-yl]methoxy]-3,5-difluorophenyl)propanoate as yellow oil

Sources & evidence

ORD record
ord-85cf42d1bdcf4485bd9d4ed2211b6fb3
Source dataset
uspto-grants-2015_06
Patent number
US09067898B1

Reaction notes

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