Sodium Carbonate → HCID 10043640, compound

HRID 2114046Notes

Reaction equation

HRID 2114046 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[O:15][CH:14]=[N:13][CH:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[O:16]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[O:15]1[C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=4[O:16][C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:3]=3)[NH:8][CH:9]=2)=[CH:12][N:13]=[CH:14]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 2773559(2-Phenoxyphenyl)boronic acidHCID 59811938HCID 59811938, compound

Product 1

HCID 10043640HCID 10043640, compoundYield 46.2%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of bromide 22 (300 mg, 1.14 mmol), 2-phenoxyphenylboronic acid (366 mg, 1.71 mmol), PdCl2(PPh3)2 (80.0 mg, 0.114 mmol), LiCl (145 mg, 3.42 mmol) and 1M Na2CO3 (2.85 mL, 2.82 mmol) in toluene (5.4 mL) and EtOH (5.4 mL) was refluxed overnight (105° C. oil bath temp.). The reaction mixture was cooled, and separated between brine (20 mL) and ethyl acetate (30 mL). The aqueous layer was extracted with ethyl acetate (2×30 mL). The combined organic solutions were dried (MgSO4) and concentrated. The resulting solid was dry loaded on a silicagel column. Fractions containing the product were eluted using ethyl acetate:hexane (1:1) (gradient elution) to give a solid which was triturated with ether to give 23 as a white solid (186 mg, 46%); 1H NMR (400 MHz, CDCl3) δ 6.94 (dd, J=8.8, 1.0 Hz, 2H), 7.05 (t, J=7.4 Hz, 1H), 7.08 (s, 1H), 7.12 (dd, J=8.1, 1.1 Hz, 1H), 7.33-7.20 (m, 3H), 7.38 (dt, J=9.2, 1.7 Hz, 1H), 7.56 (dd, J=7.6, 1.8 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 7.85 (s, 1H), 8.32 (d, J=2.0 Hz, 1H), 8.59 (d, J=2.0 Hz, 1H), 9.35-9.20 (bs, NH).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customseparated between brine (20 mL) and ethyl acetate (30 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×30 mL)
  4. dry with materialThe combined organic solutions were dried (MgSO4)
  5. concentrationconcentrated
  6. customThe resulting solid was dry
  7. additionFractions containing the product
  8. washwere eluted
  9. customto give a solid which
  10. customwas triturated with ether

Sources & evidence

ORD record
ord-9dde2d83d59540ddb71ea396cbd58c5d
Source dataset
uspto-grants-2008_10
Patent number
US07432375B2

Reaction notes

Loading…