Sodium Carbonate → 6-Fluoro-5-(5-hydroxymethyl-pyridin-3-yl)-3-methyl-3H-benzooxazol-2-one

HRID 1253923Notes

Reaction equation

HRID 1253923 reaction equation
[F:1][C:2]1[C:12](B2OC(C)(C)C(C)(C)O2)=[CH:11][C:5]2[N:6]([CH3:10])[C:7](=[O:9])[O:8][C:4]=2[CH:3]=1.Br[C:23]1[CH:24]=[C:25]([CH2:29][OH:30])[CH:26]=[N:27][CH:28]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CO.C(Cl)Cl.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>[F:1][C:2]1[C:12]([C:23]2[CH:28]=[N:27][CH:26]=[C:25]([CH2:29][OH:30])[CH:24]=2)=[CH:11][C:5]2[N:6]([CH3:10])[C:7](=[O:9])[O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2784733(5-Bromo-3-pyridinyl)methanolHCID 667979276-fluoro-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]oxazol-2(3H)-one

Product 1

HCID 667980446-Fluoro-5-(5-hydroxymethyl-pyridin-3-yl)-3-methyl-3H-benzooxazol-2-oneYield 44.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-Fluoro-3-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3H-benzooxazol-2-one (352 mg, 1.2 mmol), (5-bromopyridin-3-yl)methanol (188 mg, 1 mmol), Na2CO3 (2 M in water, 1 mL, 2 mmol), polymer bound Pd(PPh3)4 (642 mg, 0.07 mmol) in DME (4 mL) was heated by microwave at 100° C. for 1.25 h. The reaction mixture was cooled to room temperature and the mixture was diluted with CH3OH/CH2Cl2 (1:1, 50 mL) and filtered through a pad of celite. The celite pad was further washed with CH2Cl2/CH3OH (50 mL). Ater concentration, the residue was purified by flash column (0-10%, v/v, CH3OH in CH2Cl2) and afforded 121.9 mg of the desired product as a white solid. ESI-MS m/z: 274.9 [M+1]+, Retention time 0.93 min; 1HNMR (MeOD, 400.342 MHz) δ 3.44 (s, 3H), 4.74 (s, 2H), 7.30 (d, J=9.7 Hz, 1H), 7.34 (d, J=6.4 Hz, 1H), 8.03 (s, 1H), 8.55 (s, 1H), 8.64 (s, 1H)

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through a pad of celite
  3. washThe celite pad was further washed with CH2Cl2/CH3OH (50 mL)
  4. concentrationAter concentration
  5. customthe residue was purified by flash column (0-10%, v/v, CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-e1fbd45bdb8341a2aab3daca90db9755
Source dataset
uspto-grants-2013_06
Patent number
US08455522B2

Reaction notes

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