1,2-Dimethoxyethane → HCID 86671312, compound

HRID 1472893Notes

Reaction equation

HRID 1472893 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[N:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:15]1[N:20]=[C:19]([CH:21]=[O:22])[C:18]([Cl:23])=[CH:17][CH:16]=1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>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.O>[Cl:23][C:18]1[CH:17]=[CH:16][C:15]([C:6]2[CH:7]=[N:8][C:3]([C:2]([F:13])([F:12])[F:1])=[CH:4][CH:5]=2)=[N:20][C:19]=1[CH:21]=[O:22]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 251342782-(Trifluoromethyl)pyridine-5-boronic AcidHCID 722123126-Bromo-3-chloro-2-pyridinecarboxaldehyde

Product 1

HCID 86671312HCID 86671312, compoundYield 57.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

Nitrogen was bubbled through a mixture of 6-(trifluoromethyl)pyridin-3-ylboronic acid (828 mg, 4.34 mmol), 6-bromo-3-chloropicolinaldehyde (956 mg, 4.34 mmol), Na2CO3 (919 mg, 8.67 mmol), DME (20 mL) and water (10 mL) for 35 minutes, followed by the addition of Pd(Ph3P)4 (75 mg, 0.065 mmol). Nitrogen for bubbled through the mixture for 10 minutes. The reaction mixture was heated overnight at 75° C., after which it was cooled to room temperature, followed by the addition of 200 mL EtOAc and washing with 200 mL water and 200 mL brine. The organic phase was separated, dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on a Grace Reveleris 40 g column, eluted with 0-50% EtOAc in Heptane (25 mL/min) to provide the title compound (715 mg, 2.494 mmol, 57.5% yield) as a yellow solid. MS (ESI+) m/z 319.0 (M+H+MeOH); 1H NMR (300 MHz, DMSO-d6) δ 10.21 (s, 1H), 9.52 (d, J=1.9, 1H), 8.82 (dd, J=8.3, 1.8, 1H), 8.48 (d, J=8.5, 1H), 8.34 (d, J=8.6, 1H), 8.11 (d, J=8.3, 1H).

Workup

  1. customNitrogen for bubbled through the mixture for 10 minutes
  2. temperatureafter which it was cooled to room temperature
  3. additionfollowed by the addition of 200 mL EtOAc
  4. washwashing with 200 mL water and 200 mL brine
  5. customThe organic phase was separated
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed on a Grace Reveleris 40 g column
  10. washeluted with 0-50% EtOAc in Heptane (25 mL/min)

Sources & evidence

ORD record
ord-1235b690ddcd4e668612aef729ed1fe8
Source dataset
uspto-grants-2015_04
Patent number
US09012651B2

Reaction notes

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