Sodium Carbonate → HCID 86663036, compound

HRID 2410783Notes

Reaction equation

HRID 2410783 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.[NH2:12][C:13]1[C:22](Br)=[N:21][C:20]([Br:24])=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16].C(=O)([O-])[O-].[Na+].[Na+]>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>[NH2:12][C:13]1[C:22]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([CH2:2][OH:1])[CH:4]=2)=[N:21][C:20]([Br:24])=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 2734662[3-(Hydroxymethyl)phenyl]boronic acidHCID 53419616Methyl 3-amino-2,6-dibromoisonicotinate

Product 1

HCID 86663036HCID 86663036, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A flask containing a mixture of 3-(hydroxymethyl)phenylboronic acid (0.88 g, 5.79 mmol), methyl 3-amino-2,6-dibromoisonicotinate (1.5 g, 4 8 mmol), tetrakistriphenylphosphine Pd(0) (0.335 g, 0.290 mmol), sodium carbonate (1.23 g, 11.6 mmol) was flushed with nitrogen and toluene (12 mL), and MeOH (4 mL) were added. The reaction was heated at reflux under nitrogen for 48 hr. It was partitioned between EtOAc and water and the organic phase was separated, washed with brine, dried with sodium sulfate, and the solvent removed. Chromatography (step gradient elution with DCM containing 0 to 15% EtOAc) afforded methyl 3-amino-6-bromo-2-(3-(hydroxymethyl)phenyl)isonicotinate (1.4 g, 4.2 mmol, 86% yield) as a yellow solid. MS (ESI) m/z 339.02 (M+H). 1H NMR (400 MHz, chloroform-d) δ ppm 7.80 (1H, s), 7.58 (1H, s), 7.40-7.55 (3H, m), 5.94 (2H, br. s.), 4.74 (2H, d, J=5.79 Hz), 3.92 (3H, s), 1.77 (1H, t, J=5.92 Hz).

Workup

  1. additionA flask containing
  2. customwas flushed with nitrogen and toluene (12 mL), and MeOH (4 mL)
  3. additionwere added
  4. temperatureThe reaction was heated
  5. temperatureat reflux under nitrogen for 48 hr
  6. customIt was partitioned between EtOAc and water
  7. customthe organic phase was separated
  8. washwashed with brine
  9. dry with materialdried with sodium sulfate
  10. customthe solvent removed
  11. washChromatography (step gradient elution with DCM containing 0 to 15% EtOAc)

Sources & evidence

ORD record
ord-0b2b43fed4684b61a6bce90b3bc612ba
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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