4-Methylumbelliferone → 7-Hydroxy-4-methyl-3,4-dihydro-2H-1-benzopyran-2-one

HRID 1593916Notes

Reaction equation

HRID 1593916 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:13])=[CH:7][C:8](=[O:12])[O:9]2)=[CH:4][CH:3]=1>C(O)(=O)C.[Pd]>[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]([CH3:13])[CH2:7][C:8](=[O:12])[O:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 52805674-Methylumbelliferone

Product 1

HCID 251119877-Hydroxy-4-methyl-3,4-dihydro-2H-1-benzopyran-2-oneYield 100%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent2×

Conditions

Temperature
30 °C

Procedure

A Parr hydrogenator (1 L) was charged with 7-hydroxy-4-methylcoumarin, i.e., Compound of formula A1, (60 g, 0.34 mol) and acetic acid (350 ml). A suspension of 10% Pd/C (6.0 g) in acetic acid (150 ml) was added and the reactor sealed, evacuated and purged with nitrogen (4×). The reactor was pressurized to 320 psi with hydrogen and stirred at 30° C. for 16 hr, at which point no hydrogen was consumed and TLC (4% methanol:chloroform) showed the clean formation of product at the expense of starting material. The reactor was evacuated, purged with nitrogen and the mixture filtered through celite. The solvent was removed to give a white solid (60.5 g, 100%). Recrystallization from ethyl acetate:hexane afforded pure product as a white solid: m.p. 109-110° C.; 1H NMR (DMSO-d6) d 1.19 (d, JJ=6.7, 3H), 2.52 (dd, JJ=15.9, 7.3, 1H), 2.84 (dd, JJ=15.9, 5.5, 1H), 3.08 (m, 1H), 6.46 (d, JJ=2.4, 1H), 6.58 (dd, JJ=8.2, 2.4, 1H), 7.10 (d, JJ=8.2, 1H), 9.66 (s, 1H); 13C (DMSO-d6) d 19.84, 27.87, 36.45, 103.17, 111.38, 118.29, 127.17, 151.45, 157.17, 168.11; m/z (EI; TMS derivatized; M+) 250; IR (neat; cm−1) 3379.6, 2969.2, 2930.2, 2871.5, 1748.0, 1630.7, 1601.4, 1518.4, 1454.89, 1352.3, 1283.9, 1249.7, 1239.9, 1152.0, 1117.8, 1078.7, 1020.1, 995.7, 942.0, 854.0, 814.9.

Workup

  1. additionwas added
  2. customthe reactor sealed
  3. customevacuated
  4. custompurged with nitrogen (4×)
  5. customwas consumed
  6. customThe reactor was evacuated
  7. custompurged with nitrogen
  8. filtrationthe mixture filtered through celite
  9. customThe solvent was removed

Sources & evidence

ORD record
ord-f4c8a5bf03fc42d48b2cb45099ec9db3
Source dataset
uspto-grants-2007_11
Patent number
US07300646B2

Reaction notes

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