Diethyl Ether → HCID 86680605, compound

HRID 1497429Notes

Reaction equation

HRID 1497429 reaction equation
[CH:1]([C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)=[O:2].[CH2:20]([Mg]Br)[CH3:21].C(OCC)C>C1COCC1>[OH:2][CH:1]([C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)[CH2:20][CH3:21]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 86680606HCID 86680606, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 86680605HCID 86680605, compoundYield 44.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl 4-(6-formylpyridin-3-yl)benzoate (500 mg, 1.9 mmol) in THF (15 mL) was cooled to 0° C., 3M Ethyl magnesium bromide in diethyl ether (1.3 mL, 3.9 mmol) was slowly added at 0° C., and the reaction mixture was stirred for 2 h at 0° C., while monitoring reaction progress by TLC. The reaction mixture was quenched with saturated NH4Cl solution (20 mL) and extracted with ethyl acetate (2×200 mL). The combined organic extracts were washed with brine solution (10 mL), the organic layer was dried over Na2SO4 and concentrated under vacuum to obtain crude product. The crude product was purified by flash chromatography (silica gel, 60-120 microns) using 15% ethyl acetate in hexane eluent to afford ethyl 4-(6-(1-hydroxypropyl)pyridin-3-yl)benzoate as a brown liquid (250 mg, 44.8% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.84 (s, 1H), 8.13-8.11 (d, 1H), 8.04 (d, 2H), 7.87 (d, 2H), 7.57 (d, 1H), 5.33 (d, 1H), 4.57-4.53 (m, 1H), 4.35-4.30 (m, 2H), 1.89-1.76 (m, 1H), 1.68-1.34 (m, 1H), 1.24 (t, 3H), 0.86 (t, 3H), LC-MS m/z calcd for [M+H]+ 286.14. found 286.2.

Workup

  1. customreaction progress by TLC
  2. customThe reaction mixture was quenched with saturated NH4Cl solution (20 mL)
  3. extractionextracted with ethyl acetate (2×200 mL)
  4. washThe combined organic extracts were washed with brine solution (10 mL)
  5. dry with materialthe organic layer was dried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customto obtain crude product
  8. customThe crude product was purified by flash chromatography (silica gel, 60-120 microns)

Sources & evidence

ORD record
ord-316e941eba444ece97afeda678e5efe1
Source dataset
uspto-grants-2015_12
Patent number
US09199975B2

Reaction notes

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