4-methylideneoxane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared following the procedure described for Compound 1b, using Compound 31e instead of Compound 1a and 4-methylenetetrahydropyran (Tetrahedron, 46(7), 2411-2424, 1990) instead of tert-butyl 4-methylenepiperidine-1-carboxylate. After the usual work-up procedure, the residue was purified by means of automated flash chromatography (SP1 ®TM-Biotage; gradient Petroleum Ether-EtOAc from 10:1 to 8:2) to give the title compound as a yellowish solid. Yield: 23.7%. The title compound was prepared After the usual work-up procedure, the residue was purified by means of automated flash chromatography (SP1 ®TM-Biotage; gradient Petroleum Ether-EtOAc from 10:1 to 8:2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Zinc was activated according to a published procedure (Synthesis 1971; 415). Hydrated copper sulfate (14 g) was dissolved in water (150 mL) and added to zinc dust (60 g). The mixture was stirred for 2 hours under nitrogen. The activated zinc was isolated by filtration, washed with acetone and dried in a vacuum oven at 100° C. prior to use. The solution of 4-methylenetetrahydro-2H-pyran from Step A was dried with sodium sulfate and magnesium sulfate and filtered through Celite® (washing the cake with ether). This removed some orange solids which had precipitated. A solution of trichloroacetyl chloride (5.00 g; 27.5 mmol) in dry ether (250 mL) was added slowly (over 4 hours) to a stirred refluxing mixture of the 4-methylenetetrahydro-2H-pyran in dry ether (250 mL) and the activated zinc (5.00 g; 76.5 mmol) under nitrogen. The mixture was stirred for 16 hours at reflux. The solution was filtered through Celite® and concentrated under reduced pressure. The material was purified by chromatography on silica gel, eluting with 10:1 hexane/ethyl acetate to give impure product (160 mg) as a colorless oil which was continued directly on to the next step. washed with acetone dried in a vacuum oven at 100° C. The solution of 4-methylenetetrahydro-2H-pyran from Step A was dried with sodium sulfate and magnesium sulfate filtered through Celite® ( washing the cake with ether) This removed some orange solids which had precipitated refluxing at reflux The solution was filtered through Celite® concentrated under reduced pressure The material was purified by chromatography on silica gel eluting with 10:1 hexane/ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to Example 101 starting from methyl-3-bromo-5-(2-oxooxazolidin-3-yl)benzoate prepared as in Example 101, 4-methylenetetrahydro-2H-pyran, isatin (commercially available) according to Scheme 2. LC/MS m/e calcd. for C25H24ClN2O6: 448, observed (M+H)+: 449.21 1HNMR (400 MHz, DMSO-d6) δppm 1.72-1.81 (m, 1 H) 1.83 (d, J=4.55 Hz, 1 H) 1.92-1.99 (m, 3 H) 2.07-2.15 (m, 1 H) 3.38-3.47 (m, 1 H) 3.51-3.57 (m, 1 H) 3.57-3.66 (m, 2 H) 3.90 (s, 3 H) 4.16 (t, J=7.83 Hz, 2 H) 4.49 (t, J=7.83 Hz, 2 H) 6.90 (d, J=7.83 Hz, 1 H) 7.08 (t, J=7.58 Hz, 1 H) 7.23 (t, J=7.71 Hz, 1 H) 7.29 (d, J=7.58 Hz, 1 H) 7.74 (s, 1 H) 7.93 (s, 1 H) 8.24 (s, 1 H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to Example 101 starting from methyl-3-bromo-5-(2-oxooxazolidin-3-yl)benzoate prepared as in Example 101, 4-methylene-tetrahydro-pyran, isatin (commercially available) according to Scheme 2. LC/MS m/e calcd. for C24H22N206: 434, observed (M+H)+: 434.21H NMR (400 MHz, DMSO-d6) δppm 1.72-1.80 (m, 1 H) 1.83 (d, J=4.29 Hz, 1 H) 1.91-2.01 (m, 3 H) 2.06-2.16 (m, 1 H) 3.36-3.44 (m, 1 H) 3.50-3.56 (m, 1 H) 3.58-3.65 (m, 2 H) 4.13-4.21 (m, 2 H) 4.48 (t, J=7.96 Hz, 2 H) 6.90 (d, J=8.08 Hz, 1 H) 7.07 (t, 1 H) 7.23 (t, 1 H) 7.29 (d, J=7.58 Hz, 1 H) 7.71 (s, 1H) 7.92 (s, 1 H) 8.19 (s, 1 H) 13.40 (s, 1 H).