Cesium carbonate → Ethyl acetate hexane

HRID 1426257Notes

Reaction equation

HRID 1426257 reaction equation
FC(F)(F)S([O:6][C:7]1N=[C:9]([CH3:21])[C:10]2C([CH:16]=1)=C[C:13](OC)=[C:12](OC)[CH:11]=2)(=O)=O.[OH:24][C:25]1[CH:26]=C(B(O)O)C=CC=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].O.C(#N)C>[CH3:16][CH2:7][O:6][C:25]([CH3:26])=[O:24].[CH3:21][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59322850HCID 59322850, compound

Product 1

HCID 21226206Ethyl acetate hexaneYield 78.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

6,7-Dimethoxy-1-methylisoquinolin-3-yl trifluoromethanesulfonate (200 mg), 3-hydroxyphenylboronic acid (157 mg, 2 eq.), Pd(OAc)2 (13 mg, 0.1 eq.), XPhos (54 mg, 0.2 eq.), and Cs2CO3 (650 mg, 3.5 eq.) were combined in a flask with 9 mL ACN and 3 mL H2O and degassed. Reaction mixture was then refluxed at 100° C. for 5 hours. Solution was cooled to room temperature then diluted with EtOAc and washed with saturated NaHCO3. Organic layer was dried over sodium sulfate and concentrated. Chromatography achieved using ISCO max gradient 50% EtOAc/hexane yielding product as white solid (78 mg, 46% yield). 1H NMR (400 MHz) (CDCl3) δ 7.66-7.63 (m, 2H), 7.38 (d, J=4 Hz, 1H), 7.20 (t, J=8 Hz, 1H), 7.17 (s, 1H), 7.00 (s, 1H), 6.73-6.71 (m, 1H), 3.95 (s, 3H), 3.94 (s, 3H), 2.87 (s, 3H). 13C NMR (100 MHz) (CDCl3) δ 156.74, 156.12, 152.88, 149.93, 149.19, 141.46, 133.56, 129.85, 122.35, 118.72, 115.49, 115.25, 114.59, 105.66, 103.87, 56.05, 56.01, 22.20. IR (thin film NaCl) 3002, 2255, 1621, 1576, 1501, 1468, 1425, 1409, 1372, 1324, 1292, 1245, 1222, 1205, 1178, 1159, 1062, 1027, 995, 973, 924, 913, 896, 878, 846, 837, 781, 762, 745, 738, 726, 691, 645.

Workup

  1. customdegassed
  2. customReaction mixture
  3. temperatureSolution was cooled to room temperature
  4. washwashed with saturated NaHCO3
  5. dry with materialOrganic layer was dried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5f248bf56b0e4189a7a081e2fbe2b7cb
Source dataset
uspto-grants-2015_01
Patent number
US08933096B2

Reaction notes

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