4-ethoxycyclohexan-1-one

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

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

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 8-Ethoxy-1,4-dioxa-spiro[4.5]decane (Compound 166F, 2 gm, 10.7 mmol) and pyridinium p-toluene sulfonate (5.4 gm, 21.5 mmol) was taken up in a 1:1 mixture of acetone and water (150 mL) and stirred at 50° C. overnight. The acetone was subsequently removed under reduced pressure and the aqueous solution was extracted with ethyl acetate. The organic layer was washed with water, dried (Na2SO4), and evaporated to give the crude material which was used in the next step without further purification. Yield: 0.8 gm (53%). 1H NMR (CDCl3, 500 MHz): δ 1.24 (t, J=7.1 Hz, 3H), 1.95 (m, 2H), 2.05 (m, 2H), 2.24 (m, 2H), 2.6 (m, 2H), 3.6 (q, J=7.1 Hz 2H), 3.7 (m, 1H). The acetone was subsequently removed under reduced pressure the aqueous solution was extracted with ethyl acetate The organic layer was washed with water dried (Na2SO4) evaporated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 8-Ethoxy-1,4-dioxa-spiro[4.5]decane (Compound 166F, 2 gm, 10.7 mmol) and pyridinium p-toluene sulfonate (5.4 gm, 21.5 mmol) was taken up in a 1:1 mixture of acetone and water (150 mL) and stirred at 50° C. overnight. The acetone was subsequently removed under reduced pressure and the aqueous solution was extracted with ethyl acetate. The organic layer was washed with water, dried (Na2SO4), and evaporated to give the crude material which was used in the next step without further purification. Yield: 0.8 gm (53%). 1H NMR (CDCl3, 500 MHz): δ 1.24 (t, J=7.1 Hz, 3H), 1.95 (m, 2H), 2.05 (m, 2H), 2.24 (m, 2H), 2.6 (m, 2H), 3.6 (q, J=7.1 Hz 2H), 3.7 (m, 1H). The acetone was subsequently removed under reduced pressure the aqueous solution was extracted with ethyl acetate The organic layer was washed with water dried (Na2SO4) evaporated

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

Procedure: The title compound was prepared as a white solid from reaction of N-azetidin-3-yl-2-(1-methyl-5-trifluoromethyl-1H-indazol-3-ylamino)-acetamide TFA salt (as prepared in Example 18, Step D) and 4-ethoxy-cyclohexanone using the procedure described in Step E of Example 1.

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

Procedure: The title compound was prepared as white solid from reaction of 1,4-dioxa-spiro[4.5]decan-8-ol and EtI (Aldrich) followed by de-protection using the procedure described in Example 34.

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

Procedure: A mixture of 5-fluoro-3-(4-piperidinyl)-1,3-benzoxazol-2(3H)-one hydrochloride D138 (0.2 g), 4-(ethyloxy)cyclohexanone (WO2007107566) (0.2 g), and Hunig's base (0.1 g) in N-methylpyrrolidone (5 mL) was stirred for 2 hours then treated with sodium triacetoxyborohydride (0.5 g) was added and stirring was continued for four days. The mixture was diluted with methanol, loaded onto a SCX column and the column was eluted with methanol followed by 2M ammonia in methanol. The methanolic ammonia fractions were evaporated and the residue was purified by high pH MDAP. Two peaks were collected and evaporated separately. The fast eluting isomer gave 3-{1-[trans-4-(ethyloxy)cyclohexyl]-4-piperidinyl}-5-fluoro-1,3-benzoxazol-2(3H)-one E52 as a white solid (7 mg). was added stirring was continued for four days the column was eluted with methanol The methanolic ammonia fractions were evaporated the residue was purified by high pH MDAP Two peaks were collected evaporated separately

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

Procedure: A mixture of 5-fluoro-3-(4-piperidinyl)-1,3-benzoxazol-2(3H)-one hydrochloride D138 (0.2 g), 4-(ethyloxy)cyclohexanone (WO2007107566) (0.2 g), and Hunig's base (0.1 g) in N-methylpyrrolidone (5 mL) was stirred for 2 hours then treated with sodium triacetoxyborohydride (0.5 g) was added and stirring was continued for four days. The mixture was diluted with methanol, loaded onto a SCX column and the column was eluted with methanol followed by 2M ammonia in methanol. The methanolic ammonia fractions were evaporated and the residue was purified by high pH MDAP. Two peaks were collected and evaporated separately. The fast eluting isomer gave 3-{1-[trans-4-(ethyloxy)cyclohexyl]-4-piperidinyl}-5-fluoro-1,3-benzoxazol-2(3H)-one E52 as a white solid (7 mg). was added stirring was continued for four days the column was eluted with methanol The methanolic ammonia fractions were evaporated the residue was purified by high pH MDAP Two peaks were collected evaporated separately

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 8-Ethoxy-1,4-dioxa-spiro[4.5]decane (Compound 166F, 2 gm, 10.7 mmol) and pyridinium p-toluene sulfonate (5.4 gm, 21.5 mmol) was taken up in a 1:1 mixture of acetone and water (150 mL) and stirred at 50° C. overnight. The acetone was subsequently removed under reduced pressure and the aqueous solution was extracted with ethyl acetate. The organic layer was washed with water, dried (Na2SO4), and evaporated to give the crude material which was used in the next step without further purification. Yield: 0.8 gm (53%). 1H NMR (CDCl3, 500 MHz): δ 1.24 (t, J=7.1 Hz, 3H), 1.95 (m, 2H), 2.05 (m, 2H), 2.24 (m, 2H), 2.6 (m, 2H), 3.6 (q, J=7.1 Hz 2H), 3.7 (m, 1H). The acetone was subsequently removed under reduced pressure the aqueous solution was extracted with ethyl acetate The organic layer was washed with water dried (Na2SO4) evaporated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 8-Ethoxy-1,4-dioxa-spiro[4.5]decane (Compound 166F, 2 gm, 10.7 mmol) and pyridinium p-toluene sulfonate (5.4 gm, 21.5 mmol) was taken up in a 1:1 mixture of acetone and water (150 mL) and stirred at 50° C. overnight. The acetone was subsequently removed under reduced pressure and the aqueous solution was extracted with ethyl acetate. The organic layer was washed with water, dried (Na2SO4), and evaporated to give the crude material which was used in the next step without further purification. Yield: 0.8 gm (53%). 1H NMR (CDCl3, 500 MHz): δ 1.24 (t, J=7.1 Hz, 3H), 1.95 (m, 2H), 2.05 (m, 2H), 2.24 (m, 2H), 2.6 (m, 2H), 3.6 (q, J=7.1 Hz 2H), 3.7 (m, 1H). The acetone was subsequently removed under reduced pressure the aqueous solution was extracted with ethyl acetate The organic layer was washed with water dried (Na2SO4) evaporated