Hydrochloric Acid → HCID 50923238, compound

HRID 1798192Notes

Reaction equation

HRID 1798192 reaction equation
C([O:3][C:4](=[O:18])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([OH:17])[CH:14]=[C:15]([CH3:16])[C:7]1=2)C.[H-].[Na+].Cl[C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1.Cl>CN(C=O)C.O>[OH:11][B:9]1[C:8]2[CH:12]=[C:13]([O:17][C:22]3[N:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH:14]=[C:15]([CH3:16])[C:7]=2[CH:6]([CH2:5][C:4]([OH:3])=[O:18])[O:10]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 744042-ChloropyrimidineHCID 58292549Ethyl 2-(1,6-dihydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate

Product 1

HCID 50923238HCID 50923238, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (1,6-dihydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester (0.5 g, 2.0 mmol) in anhydrous DMF (10 mL) were added NaH (0.240 g, 6.0 mmol, 60% in mineral oil) and 2-chloro-pyrimidine (0.275 g, 2.4 mmol) at 0° C. After stirring at room temperature for 16 hours, the reaction mixture was cooled to 0° C., diluted with water (20 mL) and acidified to pH 2 with dilute hydrochloric acid. The mixture was extracted with ethyl acetate and the organic extract washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in MeOH (10 mL) and aqueous LiOH (1N, 5 mL) was added at 0° C. After stirring at room temperature for 1 hour, the mixture was acidified to pH 3 using dilute hydrochloric acid and concentrated. The residue was purified by silica gel flash column chromatography (DCM/MeOH/AcOH=10:1:trace) to give the product (0.132 g, 22.0%). mp 118-120° C. 1HNMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 8.65 (d, J=4.68 Hz, 2H), 7.22-7.45 (m, 2H), 7.11 (s, 1H), 5.53 (dd, J=9.51, 1.90 Hz, 1H), 3.10 (dd, J=15.66, 2.49 Hz, 1H), 2.31 (s, 3H), 2.15 (dd, J=15.52, 9.66 Hz, 1H). MS (ESI) m/z=301 [M+H]+.

Workup

  1. temperaturethe reaction mixture was cooled to 0° C.
  2. extractionThe mixture was extracted with ethyl acetate
  3. extractionthe organic extract
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in MeOH (10 mL)
  8. additionaqueous LiOH (1N, 5 mL) was added at 0° C
  9. stirringAfter stirring at room temperature for 1 hour
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel flash column chromatography (DCM/MeOH/AcOH=10:1:trace)

Sources & evidence

ORD record
ord-9b052cb541ef4e49a7823551dcb69f70
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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