2-propan-2-yloxyethanol

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:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dimethyl 4-nitro-1H-pyrazole-3,5-dicarboxylate (11.4 g, 50 mmol) was dissolved in tetrahydrofuran (200 mL) and the solution treated with triphenylphosphine (14.4 g, 55 mmol) and 2-isopropoxyethanol (6.36 mL, 55 mmol). The mixture was cooled on an ice bath to 0° C. and diisopropyl azodicarboxylate (10.8 mL, 55 mmol) added dropwise over 10 minutes, keeping the temperature between 20° C. and 30° C. The reaction mixture was then stirred at room temperature for 30 minutes. The reaction mixture was concentrated in vacuo and the crude product azeotroped with dichloromethane to yield the title product. 1H NMR (CDCl3, 400 MHz) δ: 1.02 (d, 6H), 3.45 (m, 1H), 3.72 (t, 2H), 3.90 (s, 3H), 3.94 (s, 3H), 4.74 (t, 2H). MS ES+ m/z 216 [MH]+ the temperature between 20° C. and 30° C The reaction mixture was concentrated in vacuo the crude product azeotroped with dichloromethane

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

Procedure: Alternately, combine 2-isopropoxyethanol (5.0 g, 48 mmol) and dichloromethane (50 mL). Cool in an ice bath. Add triethylamine (10.7 g, 105 mmol). Add dropwise methanesulfonyl chloride (1.43 g, 9.6 mmol). After 2 hours, dilute the reaction mixture with dichloromethane and extract with 1 M hydrochloric acid solution, a saturated aqueous solution of sodium bicarbonate, and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Distill the residue at reduced pressure to give 2-(isopropoxy)ethyl mesylate. Cool in an ice bath extract with 1 M hydrochloric acid solution Dry the organic layer over Na2SO4 filter evaporate in vacuo to give a residue Distill the residue at reduced pressure

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

Procedure: Combine 2-isopropoxyethanol (1.0 g, 9.6 mmol), N,N-diisopropylethylamine (2.73 g, 21.12 mmol), and dichloromethane (20 mL). Cool in an ice bath. Add dropwise methanesulfonyl chloride (1.43 g, 9.6 mmol). After 2 hours, dilute the reaction mixture with dichloromethane and extract with 1 M hydrochloric acid solution, a saturated solution of sodium bicarbonate, and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Distill the residue to give 2-(isopropoxy)ethyl mesylate: bp; 84° C. at 0.1 mm Hg. Cool in an ice bath extract with 1 M hydrochloric acid solution Dry the organic layer over Na2SO4 filter evaporate in vacuo to give a residue Distill the residue

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 synthesized as described for Intermediate example I-92 in 51% yield starting from ethyl 6-chloronicotinate and 2-isopropoxyethanol; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.70 (dd, 1 H), 8.13 (dd, 1 H), 6.91 (dd, 1 H), 4.39-4.43 (m, 2 H), 3.67-3.71 (m, 2 H), 3.55-3.65 (m, 1 H), 1.09 (d, 6 H); MS (APPI/APCI) m/z 226[M+H+].