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

HRID 1253919Notes

Reaction equation

HRID 1253919 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[CH:8]([OH:10])[CH3:9].[CH3:11][N:12]1[C:16]2[CH:17]=[C:18](B3OC(C)(C)C(C)(C)O3)[CH:19]=[CH:20][C:15]=2[O:14][C:13]1=[O:30].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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>[OH:10][CH:8]([C:7]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:18]1[CH:19]=[CH:20][C:15]2[O:14][C:13](=[O:30])[N:12]([CH3:11])[C:16]=2[CH:17]=1)[CH3:9]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 595350693-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(3H)-benzoxazoloneHCID 667978531-(3-Bromopyridin-4-yl)ethanol

Product 1

HCID 667873455-(4-(1-hydroxyethyl)pyridin-3-yl)-3-methylbenzo[d]oxazol-2(3H)-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-(3-Bromo-pyridin-4-yl)-ethanol (240 mg, 1.188 mmol), 3-Methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3H-benzooxazol-2-one (327 mg, 1.188 mmol), PalladiumTetrakis (270 mg, 0.030 mmol), sodium carbonate (2 M in water, 0.594 ml, 1.188 mmol) in 1,4-Dioxane (2 ml) was heated by microwave at 100° C. for 1 hr. After filtration, drying over Na2SO4, filtration again and concentration, the residue was purified by flash column (CH2Cl2-MeOH, v/v, 1%-4.5%) yielded an oil which was subsequently purified by chiral HPLC (Ethanol-Heptane, v/v, 20%, ChiralPak OD-H column) to peak 1 (enantiomer 1 retention time 9.21 min) and second peak (enantiomer 2, retention time 11.31 min). ESI-MS m/z: 271.2 [M+1]+, Retention time 0.93 min; 1H NMR (400.3 MHz, MeOD): δ 1.32 (d, J=6.4 Hz, 3H), 3.47 (s, 3H), 497 (q, J=6.4 Hz, 1H), 7.15 (dd, J=8.0, 2.0 Hz, 1H), 7.22 (d, J=2.0 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 7.75 (d, J=5.6 Hz, 1H), 8.38 (s, 1H), 8.59 (d, J=5.6 Hz, 1H).

Workup

  1. filtrationAfter filtration
  2. dry with materialdrying over Na2SO4, filtration again
  3. concentrationconcentration
  4. customthe residue was purified by flash column (CH2Cl2-MeOH, v/v, 1%-4.5%)
  5. customyielded an oil which
  6. customwas subsequently purified by chiral HPLC (Ethanol-Heptane, v/v, 20%, ChiralPak OD-H column) to peak 1 (enantiomer 1 retention time 9.21 min) and second peak (enantiomer 2, retention time 11.31 min)

Sources & evidence

ORD record
ord-2d3cb08a88064c8a833d5a6848bf6f76
Source dataset
uspto-grants-2013_06
Patent number
US08455522B2

Reaction notes

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