Cesium carbonate → HCID 86730081, compound

HRID 880024Notes

Reaction equation

HRID 880024 reaction equation
[OH:1][C:2]1[C:3](=[O:13])[NH:4][CH:5]=[CH:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:21][CH:22]1[CH2:24][CH2:23]1>CN(C=O)C.CCOC(C)=O>[CH:22]1([CH2:21][N:4]2[CH:5]=[CH:6][C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:2]([OH:1])[C:3]2=[O:13])[CH2:24][CH2:23]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 81503BromomethylcyclopropaneHCID 54697099Ethyl 3-hydroxy-2-oxo-1,2-dihydropyridine-4-carboxylate

Product 1

HCID 86730081HCID 86730081, compoundYield 25.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Intermediate 1B (250 mg, 1.370 mmol) in DMF (2 mL) was added cesium carbonate (1.12 g, 3.41 mmol) and (bromomethyl)cyclopropane (553 mg, 4.09 mmol). The reaction was heated at 80° C. for 3 h. The reaction mixture was diluted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was dissolved in a small amount of DCM and charged to a 24 g silica gel cartridge which was eluted with a 25 min gradient from 0-100% EtOAc/hexane to give Intermediate 11 (82 mg, 0.350 mmol, 25.3% yield) as an oil. HPLC/MS (Method D) RT=1.64 min, [M+1]+ 238.1; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.20 (1H, d, J=7.28 Hz), 6.30 (1H, d, J=7.03 Hz), 4.21 (2H, q, J=7.03 Hz), 3.65-3.66 (2H, m), 1.29 (1H, m), 1.19 (3H, t, J=7.04 Hz), 0.78 (2H, m), 0.61 (2H, m).

Workup

  1. washwashed with brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in a small amount of DCM
  6. additioncharged to a 24 g silica gel cartridge which
  7. washwas eluted with a 25 min gradient from 0-100% EtOAc/hexane

Sources & evidence

ORD record
ord-9fb15f31d0cd46dfa356b3f0222623bd
Source dataset
uspto-grants-2015_03
Patent number
US08993557B2

Reaction notes

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