Tetrahydro-2-(2-propynyloxy)-2H-pyran → 1-(3,4-Dichlorophenyl)-4-[(oxan-2-yl)oxy]but-2-yn-1-one

HRID 1823236Notes

Reaction equation

HRID 1823236 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[Cl:14])[C:5](N(OC)C)=[O:6].[CH2:15]([O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[C:16]#[CH:17].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:5](=[O:6])[C:17]#[C:16][CH2:15][O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[CH:11]=[CH:12][C:13]=1[Cl:14]

Participants

5

Reactant 3

HCID 98609Tetrahydro-2-(2-propynyloxy)-2H-pyranHCID 2733832Lithium HexamethyldisilazideHCID 114136423,4-Dichloro-N-methoxy-N-methylbenzamide

Product 1

HCID 221710771-(3,4-Dichlorophenyl)-4-[(oxan-2-yl)oxy]but-2-yn-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

To a mixture of 3,4-dichloro-N-methoxy-N-methyl-benzamide from Example 511 (0.68 g, 2.9 mmol) and tetrahydro-2-(2-propynyloxy)-2H-pyran (0.40 mL, 2.9 mmol) in 3.5 mL of dry THF at −25° C. was added lithium bis(trimethylsilyl)amide (LHMDS, 1 M in THF) between −25° C. and −18° C. The reaction mass was stirred at that temperature range for 1 h. The reaction was quenched with 10 mL of 1 M citric acid and was allowed to warm to 10° C. EtOAc (5 mL) was added and the mass was stirred for 15 min. The pH of the aqueous layer was 5. The layers were separated and the organic layer was concentrated to give a light yellow oil (110%, including residual solvent). HPLC (Method U): Rt=15.42 min. MS (ES+): mass calculated for C15H14Cl2O3, 312.03; m/z found, 325.1 [M+Na]+. 1H NMR (400 MHz, CDCl3): 8.19 (d, J=2 Hz, 1H), 7.95 (dd, J=8.4, 2.1 Hz, 1H), 7.57 (d, J=8.4 Hz, 1H), 4.94-4.81 (m, 1H), 4.56 (s, 2H), 3.97-3.82 (m, 1H), 3.71-3.55 (m, 1H), 1.91-1.54 (m, 6H). 13C NMR (100 MHz, CDCl3): 175.0, 139.0, 136.0, 133.4, 131.4, 131.2, 130.8, 128.3, 97.7, 92, 82.9, 62.2, 54.2, 30.1, 25.2, 18.9.

Workup

  1. customThe reaction was quenched with 10 mL of 1 M citric acid
  2. additionEtOAc (5 mL) was added
  3. stirringthe mass was stirred for 15 min
  4. customThe layers were separated
  5. concentrationthe organic layer was concentrated
  6. customto give a light yellow oil (110%, including residual solvent)

Sources & evidence

ORD record
ord-75fa69f2d38e44a880f35f940fc1c2eb
Source dataset
uspto-grants-2006_05
Patent number
US07037931B2

Reaction notes

Loading…