Sodium Carbonate → 5-(4-(1-methoxyethyl)pyridin-3-yl)-3-methylbenzo[d]oxazol-2(3H)-one

HRID 1253951Notes

Reaction equation

HRID 1253951 reaction equation
[CH3:1][N:2]1[C:6]2[CH:7]=[C:8](B3OC(C)(C)C(C)(C)O3)[CH:9]=[CH:10][C:5]=2[O:4][C:3]1=[O:20].Br[C:22]1[CH:23]=[N:24][CH:25]=[CH:26][C:27]=1[CH:28]([O:30][CH3:31])[CH3:29].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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>[CH3:31][O:30][CH:28]([C:27]1[CH:26]=[CH:25][N:24]=[CH:23][C:22]=1[C:8]1[CH:9]=[CH:10][C:5]2[O:4][C:3](=[O:20])[N:2]([CH3:1])[C:6]=2[CH:7]=1)[CH3:29]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 595350693-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(3H)-benzoxazoloneHCID 667980463-Bromo-4-(1-methoxy-ethyl)-pyridine

Product 1

HCID 667976675-(4-(1-methoxyethyl)pyridin-3-yl)-3-methylbenzo[d]oxazol-2(3H)-oneYield 69%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-Methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3H-benzooxazol-2-one (255 mg, 0.93 mmol), 3-Bromo-4-(1-methoxy-ethyl)-pyridine (200 mg, 0.93 mmol), Na2CO3 (2 M in water, 1.6 mL, 0.8 mmol) and PdCl2(PPh3)2 (52 mg, 0.07 mmol) in DMF (3 was heated at 100″C for overnight. After concentration, the residue was diluted in DCM and saturated NH4Cl solution. After filtration and extraction, the combined extracts were dried over anhydrous Na2SO4. After filtration and concentration, the residue was purified by flash column (MeOH—CH2Cl2, v/v, 0-1.5%) to give the title compound (182 mg, 69%). The racemate was resolved by chiral HPLC (ChiralPak, IA-H column, 40% EtOH/Heptane) to the first peak (enantiomer 1, retention time=10.90 min) and the second peak (enantiomer 2, retention time 14.25 min). ESI-MS m/z: 285 [M+1]+, Retention time 1.13 min; 1HNMR (MeOD, 400 MHz) δ 1.38 (d, J=6.8 Hz, 3H), 3.30 (s, 3H), 3.48 (s, 3H), 4.69 (q, J=6.8 Hz, 1H), 7.27 (dd, J=8.0, 1.6 Hz, 1H), 7.32 (d, J=1.6 Hz, 1H), 7.45 (d, J=8.0 Hz, 1H), 8.25 (d, J=6.0 Hz, 1H), 8.78 (s, 1H), 8.89 (id, J=6.0 z, 1H).

Workup

  1. temperaturewas heated at 100″C for overnight
  2. concentrationAfter concentration
  3. additionthe residue was diluted in DCM
  4. filtrationAfter filtration and extraction
  5. dry with materialthe combined extracts were dried over anhydrous Na2SO4
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified by flash column (MeOH—CH2Cl2, v/v, 0-1.5%)

Sources & evidence

ORD record
ord-b4e91ec02bd343038e18d9826fc69874
Source dataset
uspto-grants-2013_06
Patent number
US08455522B2

Reaction notes

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