2-bromo-4-methyl-5-(trifluoromethyl)benzaldehyde

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

Procedure: To a solution of 2-bromo-4-methyl-5-trifluoromethylbenzaldehyde (100 mg, 0.374 mmol) in DMF (3 mL) was added methyl 4-(2-oxo-1-oxa-3,8-diazaspiro[4.5]dec-3-yl)benzoate (122 mg, 0.374 mmol) (from Example 1-1, Step 2) and DIPEA (0.326 mL, 1.87 mmol). The mixture was stirred at room temperature for 15 minutes and then acetic acid (0.107 mL, 1.87 mmol) and sodium triacetoxyborohydride (120 mg, 0.562 mmol) were added. The reaction was stirred at room temperature and was followed by LC/MS until complete. Water was added and the mixture was extracted twice with ethyl acetate. The organic layers were combined and dried over sodium sulfate and evaporated. The residue was purified on silica gel (CombiFlash 4 gm pre-packed column) eluting with a 10-30% ethyl acetate/hexanes gradient to afford the title intermediate (130 mg) as a white solid. The reaction was stirred at room temperature the mixture was extracted twice with ethyl acetate dried over sodium sulfate evaporated The residue was purified on silica gel (CombiFlash 4 gm pre-packed column) eluting with a 10-30% ethyl acetate/hexanes gradient

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

Procedure: To a solution of 2-bromo-4-methyl-5-trifluoromethylbenzaldehyde (100 mg, 0.374 mmol) in DMF (3 mL) was added methyl 4-(2-oxo-1-oxa-3,8-diazaspiro[4.5]dec-3-yl)benzoate (122 mg, 0.374 mmol) (from Example 1-1, Step 2) and DIPEA (0.326 mL, 1.87 mmol). The mixture was stirred at room temperature for 15 minutes and then acetic acid (0.107 mL, 1.87 mmol) and sodium triacetoxyborohydride (120 mg, 0.562 mmol) were added. The reaction was stirred at room temperature and was followed by LC/MS until complete. Water was added and the mixture was extracted twice with ethyl acetate. The organic layers were combined and dried over sodium sulfate and evaporated. The residue was purified on silica gel (CombiFlash 4 gm pre-packed column) eluting with a 10-30% ethyl acetate/hexanes gradient to afford the title intermediate (130 mg) as a white solid. The reaction was stirred at room temperature the mixture was extracted twice with ethyl acetate dried over sodium sulfate evaporated The residue was purified on silica gel (CombiFlash 4 gm pre-packed column) eluting with a 10-30% ethyl acetate/hexanes gradient

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

Procedure: To a solution of 2-bromo-4-methyl-5-trifluoromethylbenzaldehyde (100 mg, 0.374 mmol) in DMF (3 mL) was added methyl 4-(2-oxo-1-oxa-3,8-diazaspiro[4.5]dec-3-yl)benzoate (122 mg, 0.374 mmol) (from Example 1-1, Step 2) and DIPEA (0.326 mL, 1.87 mmol). The mixture was stirred at room temperature for 15 minutes and then acetic acid (0.107 mL, 1.87 mmol) and sodium triacetoxyborohydride (120 mg, 0.562 mmol) were added. The reaction was stirred at room temperature and was followed by LC/MS until complete. Water was added and the mixture was extracted twice with ethyl acetate. The organic layers were combined and dried over sodium sulfate and evaporated. The residue was purified on silica gel (CombiFlash 4 gm pre-packed column) eluting with a 10-30% ethyl acetate/hexanes gradient to afford the title intermediate (130 mg) as a white solid. The reaction was stirred at room temperature the mixture was extracted twice with ethyl acetate dried over sodium sulfate evaporated The residue was purified on silica gel (CombiFlash 4 gm pre-packed column) eluting with a 10-30% ethyl acetate/hexanes gradient

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

Procedure: To a solution of 2-bromo-4-methyl-5-trifluoromethylbenzaldehyde (100 mg, 0.374 mmol) in DMF (3 mL) was added methyl 4-(2-oxo-1-oxa-3,8-diazaspiro[4.5]dec-3-yl)benzoate (122 mg, 0.374 mmol) (from Example 1-1, Step 2) and DIPEA (0.326 mL, 1.87 mmol). The mixture was stirred at room temperature for 15 minutes and then acetic acid (0.107 mL, 1.87 mmol) and sodium triacetoxyborohydride (120 mg, 0.562 mmol) were added. The reaction was stirred at room temperature and was followed by LC/MS until complete. Water was added and the mixture was extracted twice with ethyl acetate. The organic layers were combined and dried over sodium sulfate and evaporated. The residue was purified on silica gel (CombiFlash 4 gm pre-packed column) eluting with a 10-30% ethyl acetate/hexanes gradient to afford the title intermediate (130 mg) as a white solid. The reaction was stirred at room temperature the mixture was extracted twice with ethyl acetate dried over sodium sulfate evaporated The residue was purified on silica gel (CombiFlash 4 gm pre-packed column) eluting with a 10-30% ethyl acetate/hexanes gradient