Sodium Carbonate → HCID 68841605, compound

HRID 1948628Notes

Reaction equation

HRID 1948628 reaction equation
I[C:2]1[C:3]([NH2:12])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH2:13]([Si:15]([CH2:23][CH3:24])([CH2:21][CH3:22])[C:16]#[C:17][CH2:18][CH2:19][OH:20])[CH3:14].[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O.CCOC(C)=O.CCOCC>[CH2:23]([Si:15]([CH2:13][CH3:14])([CH2:21][CH3:22])[C:16]1[NH:12][C:3]2=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=[C:2]2[C:17]=1[CH2:18][CH2:19][OH:20])[CH3:24]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27606944-(Triethylsilyl)-3-butyn-1-olHCID 153509143-Iodo-5-(trifluoromethyl)pyridin-2-amine

Product 1

HCID 68841605HCID 68841605, compound

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 21584169Diethylether ethylacetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-iodo-5-(trifluoromethyl)pyridin-2-amine (13 g, 45.1 mmole), 4-(triethylsilyl)but-3-in-1-ol (12.4 g, 67.7 mmole), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane (1.78 g, 2.26 mmole), lithium chloride (1.86 g, 45.1 mmole) and sodium carbonate (9.54 g, 90.3 mmole) in DMF (460 ml) was stirred under nitrogen for 15 hours at 100° C. The reaction mixture was cooled to RT, 2 l of EtOAc/ether (1:1) were added, and the mixture was poured into 2 l of H2O. The two-phase suspension was filtered through filter earth. After separating the phases the aqueous phase was extracted with EtOAc (2×1 l). The organic phases were combined and washed with H2O and with saturated NaCl solution and dried over MgSO4. After filtering the drying agent the solvents were removed on a rotary evaporator. The residue was purified by column chromatography (tert.-butyl methyl ether/n-hexane=2:3). The mixed fraction thereby obtained was taken up 4 times, each time with 20 ml of dichloromethane and suction filtered from the white crystalline solid. The first three fractionated precipitates were combined: 2-(2-(triethylsilyl)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanol was obtained (3.8 g, 24.4%).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. filtrationThe two-phase suspension was filtered
  3. filtrationthrough filter earth
  4. customAfter separating the phases the aqueous phase
  5. extractionwas extracted with EtOAc (2×1 l)
  6. washwashed with H2O and with saturated NaCl solution
  7. dry with materialdried over MgSO4
  8. filtrationAfter filtering the drying agent the solvents
  9. customwere removed on a rotary evaporator
  10. customThe residue was purified by column chromatography (tert.-butyl methyl ether/n-hexane=2:3)
  11. customThe mixed fraction thereby obtained
  12. filtrationeach time with 20 ml of dichloromethane and suction filtered from the white crystalline solid
  13. customThe first three fractionated precipitates

Sources & evidence

ORD record
ord-99ba0a82541645bd9877bf2a6c1f3807
Source dataset
uspto-grants-2013_03
Patent number
US08399503B2

Reaction notes

Loading…