2-methylbutan-2-yl acetate

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

Procedure: (S)-ethyl 2-(6-cyano-3-methyl-1(trifluoromethylsulfonyloxy)-naphthalen-2-yl)-2-(tert-pentyloxy)acetate was prepared in a similar way to (S)-ethyl 2-tert-butoxy-2-(6-cyano-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate in Example 5 except tert-amyl acetate was used instead of tert-butyl acetate. 1H NMR (400 MHz, CDCl3) 8.18 (s, 1H), 8.13 (d, J=8.7 Hz, 1H), 7.73 (s, 1H), 7.71 (d, J=8.9 Hz, 1H), 5.73 (s, 1H), 4.27-4.08 (m, 2H), 2.59 (s, 3H), 1.62-1.43 (m, 2H), 1.20 (s, 3H), 1.17 (t, J=7.2 Hz, 3H), 1.08 (s, 3H), 0.77 (t, J=7.4 Hz, 3H).

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

Procedure: (S)-ethyl 2-(6-cyano-3-methyl-1(trifluoromethylsulfonyloxy)-naphthalen-2-yl)-2-(tert-pentyloxy)acetate was prepared in a similar way to (S)-ethyl 2-tert-butoxy-2-(6-cyano-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate in Example 5 except tert-amyl acetate was used instead of tert-butyl acetate. 1H NMR (400 MHz, CDCl3) 8.18 (s, 1H), 8.13 (d, J=8.7 Hz, 1H), 7.73 (s, 1H), 7.71 (d, J=8.9 Hz, 1H), 5.73 (s, 1H), 4.27-4.08 (m, 2H), 2.59 (s, 3H), 1.62-1.43 (m, 2H), 1.20 (s, 3H), 1.17 (t, J=7.2 Hz, 3H), 1.08 (s, 3H), 0.77 (t, J=7.4 Hz, 3H).

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

Procedure: Methyl (2S)-2-[(2-methylbutan-2-yl)oxy 1-24(228)-4,17,22,28-tetramethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33), 11, 13, 15 (20),16,18-decaen-3-yl]acetate: To a stirred solution of methyl (2S)-2-hydroxy-2-[(22S)-4,17,22,28-tetramethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate (50 mg, 0.084 mmol) in DCM (2 mL) and tert-pentyl acetate (0.692 mL, 5.85 mmol) at rt was added 70 wt % perchloric acid (0.022 mL, 0.251 mmol). After 3 h, the reaction mixture was diluted with DCM (25 mL), carefully quenched with sat. NaHCO3 (5 mL), organic layer separated and washed with brine (10 mL), dried (Na2SO4), filtered and concentrated to give yellow liquid. This was purified by flash column chromatograpgy on silica gel column using (10-50% EtOAc/Hex as eluant) to afford the desired methyl (25)-2-[(2-methylbutan-2-yl)oxy]-2-[(22S)-4,17,22,28-tetramethyl-21,27-dioxa-1,5,7,8-tetraazahexacyclo[26.2.2.16,9.110,14.02,7.015,20]tetratriaconta-2,4,6(34),8,10(33),11,13,15(20),16,18-decaen-3-yl]acetate (10 mg, 0.015 mmol, 17.90% yield) as viscous oil. 1H NMR (500 MHz, CDCl3) δ 7.82-7.76 (m, 1H), 7.50 (t, J=7.7 Hz, 1H), 7.39-7.34 (m, 1H), 7.18 (d, J=1.9 Hz, 1H), 7.13 (dd, J=8.5, 2.0 Hz, 1H), 6.92 (d, J=8.5 Hz, 1H), 6.90 (s, 1H), 5.90 (s, 1H), 4.66-4.59 (m, 1H), 4.58-4.52 (m, 1H), 3.84-3.79 (m, 1H), 3.77 (s, 3H), 3.50 (td, J=7.7, 3.1 Hz, 1H), 3.44-3.35 (m, 1H), 3.27 (d, J=12.3 Hz, 1H), 2.89 (d, J=11.3 Hz, 1H), 2.61 (s, 3H), 2.36 (s, 3H), 2.07-1.96 (m, 3H), 1.89-1.80 (m, 1H), 1.79-1.70 (m, 3H), 1.63-1.47 (m, 6H), 1.26 (s, 3H), 1.23 (s, 3H), 1.17 (d, J=6.0 Hz, 3H), 1.15 (s, 3H), 0.83 (t, J=7.5 Hz, 3H). LCMS (M+H)=669.4. 35 mg of starting material was also recovered. carefully quenched with sat. NaHCO3 (5 mL), organic layer separated washed with brine (10 mL) dried (Na2SO4) filtered concentrated to give yellow liquid This was purified by flash column chromatograpgy on silica gel column

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

Procedure: To a solution of 2-methylbutan-2-ol (10 g, 113 mmol) in DCM (100 mL) was added DMAP (0.693 g, 5.67 mmol) and TEA (17.39 mL, 125 mmol). Mixture was then cooled to 0° C. and acetic anhydride (15.56 mL, 125 mmol) was added and the mixture was stirred at room temp for 24 h. The mixture was then washed with sat.NaHCO3 (100 mL), 1N HCl (100 mL), 10% NaOH (100 mL), brine (100 mL), dried (Na2SO4), filtered and concentrated to afford dark oil which was dilstilled by short path distillation (product distilled at 90-95° C.) to afford tert-pentyl acetate (8 g, 61.5 mmol, 54.2% yield) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 1.98 (s, 3H), 1.78 (q, J=7.5 Hz, 2H), 1.43 (s, 6H), 0.89 (t, J=7.5 Hz, 3H). The mixture was then washed NaHCO3 (100 mL), 1N HCl (100 mL), 10% NaOH (100 mL), brine (100 mL), dried (Na2SO4) filtered concentrated to afford dark oil which was dilstilled by short path distillation (product distilled at 90-95° C.)

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

Procedure: (S)-ethyl 2-(6-cyano-3-methyl-1(trifluoromethylsulfonyloxy)-naphthalen-2-yl)-2-(tert-pentyloxy)acetate was prepared in a similar way to (S)-ethyl 2-tert-butoxy-2-(6-cyano-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate in Example 5 except tert-amyl acetate was used instead of tert-butyl acetate. 1H NMR (400 MHz, CDCl3) 8.18 (s, 1H), 8.13 (d, J=8.7 Hz, 1H), 7.73 (s, 1H), 7.71 (d, J=8.9 Hz, 1H), 5.73 (s, 1H), 4.27-4.08 (m, 2H), 2.59 (s, 3H), 1.62-1.43 (m, 2H), 1.20 (s, 3H), 1.17 (t, J=7.2 Hz, 3H), 1.08 (s, 3H), 0.77 (t, J=7.4 Hz, 3H).