Oxalyl chloride → Methyl 1-(4-oxochroman-6-yl)cyclopropanecarboxylate

HRID 1964247Notes

Reaction equation

HRID 1964247 reaction equation
[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]([OH:19])=O)=[CH:10][CH:9]=2)[CH2:7][CH2:6]1)=[O:4].C(Cl)(=O)C(Cl)=O>C(Cl)Cl.CN(C=O)C>[O:19]=[C:17]1[C:10]2[C:11](=[CH:12][CH:13]=[C:8]([C:5]3([C:3]([OH:2])=[O:4])[CH2:6][CH2:7]3)[CH:9]=2)[O:14][CH2:15][CH2:16]1.[O:19]=[C:17]1[C:10]2[C:11](=[CH:12][CH:13]=[C:8]([C:5]3([C:3]([O:2][CH3:1])=[O:4])[CH2:6][CH2:7]3)[CH:9]=2)[O:14][CH2:15][CH2:16]1

Participants

6

Reactant 2

HCID 65578Oxalyl chlorideHCID 59129343HCID 59129343, compound

Product 2

HCID 591291561-(4-Oxochroman-6-yl)cyclopropanecarboxylic acidYield 19%HCID 59129225Methyl 1-(4-oxochroman-6-yl)cyclopropanecarboxylateYield 38%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
2.5 °C

Procedure

To a solution of 1-[4-(2-carboxy-ethoxy)-phenyl]-cyclopropanecarboxylic methyl ester (5.0 g, 20 mmol) in CH2Cl2 (50 mL) were added oxalyl chloride (4.8 g, 38 mmol) and two drops of DMF at 0° C. The mixture was stirred at 0-5° C. for 1 h and then evaporated under vacuum. To the resulting mixture was added CH2Cl2 (50 mL) at 0° C. and stirring was continued at 0-5° C. for 1 h. The reaction was slowly quenched with water and was extracted with EtOAc (50 mL×3). The combined organic extracts were dried over anhydrous Na2SO4 and evaporated under vacuum to give the crude product, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 20:1-2:1) to give 1-(4-oxochroman-6-yl)cyclopropanecarboxylic acid (830 mg, 19%) and methyl 1-(4-oxochroman-6-yl)cyclopropanecarboxylate (1.8 g, 38%). 1-(4-Oxochroman-6-yl)cyclopropane-carboxylic acid: 1H NMR (400 MHz, DMSO) δ 12.33 (br s, 1 H), 7.62 (d, J=2.0 Hz, 1 H), 7.50 (dd, J=2.4, 8.4 Hz, 1 H), 6.95 (d, J=8.4 Hz, 1 H), 4.50 (t, J=6.4 Hz, 2 H), 2.75 (t, J=6.4 Hz, 2 H), 1.44-1.38 (m, 2 H), 1.10-1.07 (m, 2H). MS (ESI) m/z (M+H+) 231.4. 1-(4-Oxochroman-6-yl)cyclopropanecarboxylate: 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J=2.4 Hz, 1 H), 7.48 (dd, J=2.4, 8.4 Hz, 1 H), 6.93 (d, J=8.4 Hz, 1 H), 4.55-4.52 (m, 2 H), 3.62 (s, 3 H), 2.80 (t, J=6.4 Hz, 2 H), 1.62-1.56 (m, 2 H), 1.18-1.15 (m, 2H).

Workup

  1. customevaporated under vacuum
  2. additionTo the resulting mixture was added CH2Cl2 (50 mL) at 0° C.
  3. stirringstirring
  4. waitwas continued at 0-5° C. for 1 h
  5. customThe reaction was slowly quenched with water
  6. extractionwas extracted with EtOAc (50 mL×3)
  7. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  8. customevaporated under vacuum
  9. customto give the crude product, which
  10. customwas purified by column chromatography on silica gel (petroleum ether/ethyl acetate 20:1-2:1)

Sources & evidence

ORD record
ord-18fc16ae152e4485bf7657e8899391d6
Source dataset
uspto-grants-2013_04
Patent number
US08415387B2

Reaction notes

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