Methanesulfonic Acid → Coumarin

HRID 1522543Notes

Reaction equation

HRID 1522543 reaction equation
O[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=C[C:6]([OH:12])=[CH:7][CH:8]=2)[CH:3]=1.CS(O)(=O)=[O:15]>C(OCC)C>[O:15]1[C:4]2[C:9](=[CH:10][CH:11]=[CH:2][CH:3]=2)[CH:8]=[CH:7][C:6]1=[O:12]

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 113972,7-Naphthalenediol

Product 1

HCID 323CoumarinYield 5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a mixture of 2,7-dihydroxynaphthalene (0.20 g, 1.3 mmol) and 1 (0.20 mg, 0.83 mmol) was added methanesulfonic acid (1.3 mL, 21 mmol) at 0° C. The clear brown solution gradually became dark orange within 4 h after which time the reaction mixture was diluted with cold (−30° C.) ethyl ether (10 mL), centrifuged (3000 rpm) at 4° C. for 20 minutes. After removing the ether by aspiration, the residual orange solid was dried under high vacuum, dissolved in H2O (3 mL), and purified by RP-HPLC using an appropriate linear gradient of acetonitrile containing 10% de-ionized water (A) and 0.1% (v/v) TFA/H2O (B) (3-50% A over 20 min. followed by a steep gradient to 100% A and equilibrium back to 3% A). The fractions containing the product were collected, concentrated, and lyophilized to give Mini401 as a white solid (5%). 1H NMR (DMSO-d6, 400 MHz): δ 10.21 (1H, s), 8.08 (1H, d, J=8.9 Hz), 7.94 (1H, d, J=8.8 Hz), 7.84 (3H, bs), 7.72 (1H, s), 7.33 (1H, d, J=8.8 Hz), 7.18 (1H, dd, J=8.8, 2.0 Hz), 6.44 (1H, s), 3.54 (2H, t, J=6.8 Hz), 3.32-3.29 (2H, m). 13C NMR (DMSO-d6, 75 MHz): δ 159.2, 157.6, 155.1, 153.0, 133.9, 131.5, 130.8, 125.3, 117.0, 115.2, 114.0, 111.9, 1079, 37.2, 33.9. LRMS (APCI+): Calc'd for C15H13NO3 255.1 m/z, measured 256.2 (MH+).

Workup

  1. customAfter removing the ether by aspiration
  2. customthe residual orange solid was dried under high vacuum
  3. dissolutiondissolved in H2O (3 mL)
  4. custompurified by RP-HPLC
  5. customover 20 min.
  6. additionThe fractions containing the product
  7. customwere collected
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-92488550bcb94d31a12011209bca3a44
Source dataset
uspto-grants-2015_07
Patent number
US09075014B2

Reaction notes

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