Pyridine → 3'-Methoxy-4'-tetrahydropyranylacetophenone

HRID 1516804Notes

Reaction equation

HRID 1516804 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.N1C=CC=CC=1.[CH3:19][C:20]([C:22]1[CH:30]=[CH:29][C:27](O)=[C:24]([O:25][CH3:26])[CH:23]=1)=[O:21].[O:31]1[CH:36]=[CH:35][CH2:34][CH2:33][CH2:32]1>C(Cl)Cl>[CH3:26][O:25][C:24]1[CH:23]=[C:22]([C:20](=[O:21])[CH3:19])[CH:30]=[CH:29][C:27]=1[CH:32]1[CH2:33][CH2:34][CH2:35][CH2:36][O:31]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 2214Acetovanillone2×HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 684983603'-Methoxy-4'-tetrahydropyranylacetophenoneYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

In an oven-dried, 500 mL round bottom flask equipped with a stir bar and an addition funnel, p-toluenesulfonic acid monohydrate (156 mg, 0.82 mmol), pyridine (66 μL, 0.82 mmol), acetovanillone (6.10 g, 36.7 mmol), and CH2Cl2 (170 mL) were combined and rapidly stirred. Dihydropyran (10 mL, 110 mmol) was diluted with 40 mL of CH2Cl2, poured into the addition funnel, and added drop wise to the acetovanillone solution over a period of 2 h. The reaction was stirred for an additional 12 h at room temperature, after which it was washed with 200 mL of 1.0 N NaOH (2×). The organic phase was dried over Na2SO4, filtered, and concentrated to a clear oil under reduced pressure. The oil crystallized upon standing to afford 4.2 g of THP-C as a white solid (46% yield). The solid was used without further purification. TLC: Rf=0.19 (hexane/EtOAc 4:1); Melting point: 67-69° C.; 1H NMR: (300 MHz, CDCl3) δ 7.52 (s, 1H), 7.50 (d, J=10 Hz, 1H), 7.13 (d, J=8 Hz, 1H), 5.50 (t, J=3 Hz, 1H), 3.90 (s, 3H), 3.89 (m, 1H), 3.59 (m, 1H), 2.54 (s, 3H), 1.95 (m, 3H), 1.63 (m, 1H); 13C NMR: (75 MHz, CDCl3) δ 197.08, 150.92, 150.12, 131.60, 123.18, 115.65, 111.29, 97.14, 62.31, 56.32, 30.33, 26.45, 25.31, 18.79; IR (ATR): 2966, 2936, 2880, 1672, 1585, 1510, 1462, 1442, 1413, 1390, 1352, 1290, 1272, 1243, 1221, 1201, 1172, 1153, 1120, 1110, 1051, 1032, 1020, 959 1046 cm−1; ESI-MS: expected, 250.1; observed, m/z 251.1 [M+H+].

Workup

  1. customIn an oven-dried, 500 mL round bottom flask equipped with a stir bar and an addition funnel
  2. additionpoured into the addition funnel
  3. stirringThe reaction was stirred for an additional 12 h at room temperature
  4. washafter which it was washed with 200 mL of 1.0 N NaOH (2×)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to a clear oil under reduced pressure
  8. customThe oil crystallized

Sources & evidence

ORD record
ord-5faa10d2cad3448e9d99c3b2e222824b
Source dataset
uspto-grants-2012_07
Patent number
US08227616B2

Reaction notes

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