oxan-2-ylmethanol

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

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

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

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

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

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

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

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: To a suspension of NaH (63.8 mg, 1.59 mmol) in THF (4 mL) at 0° C. under argon was added tetrahydro-2H-pyran-2-ylmethanol (92.5 mg, 0.80 mmol). The mixture was maintained at 0° C. for 20 minutes, at which time 2-bromo-6-(bromomethyl)pyridine (Example 190, Step 1) (200 mg, 0.80 mmol) was added. The reaction allowed to warm to room temperature and then heated to 55° C. overnight. The reaction was then cooled to ambient temperature and quenched by the addition of water. The quenched reaction mixture was diluted with water (10 mL) and DCM (10 mL) and shaken. The suspensions were passed through disposable phase separators and the DCM eluent was captured and evaporated to dryness to afford the title compound which was used without further purification. was added heated to 55° C. overnight The reaction was then cooled to ambient temperature quenched by the addition of water The quenched reaction mixture evaporated to dryness

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

Procedure: A stirred solution of 13.9 g of tetrahydro-2-pyranylmethanol and 18.2 g of triethylamine in 250 ml of methylene chloride was cooled to -10° C. and 15.1 g of methansulfonyl chloride was added dropwise over 5 minutes while maintaining the temperature at -10° C. to 0° C. using a cooling bath. The bath was removed and the mixture was stirred for 1/2 hour while the temperature reached 16° C. The reaction mixture was washed successively with 150 ml of ice water, 150 ml of 10% hydrochloric acid solution, 150 ml of saturated sodium bicarbonate solution and 150 ml of saturated sodium chloride solution, then dried (MgSO4) and evaporated under vacuum at 50° C. to give 23.7 g of a yellow oil, which was Claisen distilled to yield 19.7 g of the desired product; b.p. 110° C. (0.2 mm). while maintaining the temperature at -10° C. to 0° C. The bath was removed reached 16° C The reaction mixture was washed successively with 150 ml of ice water, 150 ml of 10% hydrochloric acid solution, 150 ml of saturated sodium bicarbonate solution and 150 ml of saturated sodium chloride solution dried (MgSO4) evaporated under vacuum at 50° C.

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