Dichloromethane → HCID 67004613, compound

HRID 1513853Notes

Reaction equation

HRID 1513853 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=[CH:6]2.[F:37][C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=1B(O)O.[Cl:48]CCl.[F-].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C>[ClH:48].[F:37][C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:39]=1[C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[C:9]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]2[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]2)=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 25953Cesium fluorideHCID 2734335(2,5-Difluorophenyl)boronic acidHCID 116133766-Methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl trifluoromethanesulfonate

Product 1

HCID 67004613HCID 67004613, compoundYield 91.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

Combine trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-yl ester (154 mg, 0.29 mmol), 2,5-difluorophenyl boronic acid (139 mg, 0.88 mmol), [1,1′-bis(diphenylphosphino)-ferrocene)dichloropalladium (II), complex with dichloromethane (1:1) (239 mg, 0.29 mmol), cesium fluoride (400 mg, 2.63 mmol) and acetonitrile (6 mL), stir and heat at 90° C. After 4 hours, cool to ambient temperature and remove solvent under vacuum. Suspend and sonicate the residue in ethyl ether, filter and remove the solvent under vacuum. Chromatograph the crude mixture on silica gel with dichloromethane/methanol mixtures, combine fractions containing product, add 1M hydrogen chloride in ether (1 mL) and remove solvent under vacuum to give 140 mg of the title compound: mass spectrum (ion spray) m/z=490 (M−Cl).

Workup

  1. temperaturecool to ambient temperature
  2. customremove solvent under vacuum
  3. customsonicate the residue in ethyl ether
  4. filtrationfilter
  5. customremove the solvent under vacuum
  6. additionChromatograph the crude mixture on silica gel with dichloromethane/methanol mixtures, combine fractions containing product
  7. additionadd 1M hydrogen chloride in ether (1 mL)
  8. customremove solvent under vacuum

Sources & evidence

ORD record
ord-b75bd819121144a7935e75aa2579e167
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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