Tetrahydrofuran → 1-(Tetrahydro-2H-pyran-4-yl)ethanone

HRID 1045985Notes

Reaction equation

HRID 1045985 reaction equation
CON(C)[C:4]([CH:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1)=[O:5].[CH2:13]1COCC1.C[Mg]Br>O.CCOC(C)=O>[C:4]([CH:6]1[CH2:7][CH2:8][O:9][CH2:10][CH2:11]1)(=[O:5])[CH3:13]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 23144693N-methoxy-N-methyloxane-4-carboxamideHCID 178418573HCID 178418573, compound

Product 1

HCID 98773651-(Tetrahydro-2H-pyran-4-yl)ethanoneYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A flask was charged with N-methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide 2 (11.7 g, 67.5 mmol) and THF (350 mL). The resulting mixture was immersed in a cooling bath at −60° C., and methylmagnesium bromide (3.0 M in ether, 33.8 mL, 101.4 mmol) was added via syringe over ˜8 min. The temperature of the bath was allowed to rise to 0° C. over 6 h. At that time, the reaction was diluted with water and EtOAc and stirred vigorously for 10 min. The phases were separated, and the aqueous layer was extracted with EtOAc. The organic portions were combined, washed with brine, dried over MgSO4, filtered, and concentrated. The crude residue was subjected to column chromatography (120 g silica, 80 mL/min, 0% to 100% EtOAc/hexanes) to give 4-acetyltetrahydro-4H-pyran 3 (7.05 g, 55.0 mmol, 81%). 1H NMR (400 MHz, CDCl3) for 3: δ 3.95 (ddd, J=11.6, 4.4, 2.8 Hz, 2 H), 3.38 (dt, Jd=2.8 Hz, Jt=11.6 Hz, 2 H), 2.50 (m, 1 H), 2.12 (s, 3 H), 1.75 (m, 2 H), 1.65 (m, 2 H). LCMS for 3 (conditions D): tR=0.83 min, m/e=129.4 (M+H, base).

Workup

  1. customThe resulting mixture was immersed in a cooling bath at −60° C.
  2. customThe phases were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-531d97c4f9f14dca9a342dab962880d9
Source dataset
uspto-grants-2013_10
Patent number
US08569310B2

Reaction notes

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