methyl heptanoate

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: In analogy to the procedure described in example 10 c], [rac]-2-(4-hydroxy-2-methyl-benzyl)-heptanoic acid methyl ester (example 126 c]) was reacted with [rac]-cyclopropyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-methanol (example 121 a]) in the presence of tributylphosphine and N,N,N′,N′-tetramethyl azodicarboxamide to yield 2-(4-cyclopropyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-methoxy}-2-methyl-benzyl)-heptanoic acid methyl ester as a mixture of two diastereomeric racemates as yellow oil.

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

Procedure: In analogy to the procedure described in example 125 a], methyl heptanoate was deprotonated with lithium diisopropylamide and reacted with 4-benzyloxy-2-methyl-benzaldehyde in tetrahydrofuran to obtain 2-[(4-benzyloxy-2-methyl-phenyl)-hydroxy-methyl]-heptanoic acid methyl ester as a mixture of two diastereomeric racemates as light yellow oil.

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

Procedure: TMPH Synthesis. To a mixture of 2,2,6,6-tetramethyl-4-piperidinol (472 mg, 3.0 mmol) and methyl heptanoate (476 mg, 3.3 mmol) in 3.0 mL of dimethyl formamide was added 250 mg of powdered potassium carbonate. The resulting mixture was heated at 145˜155° C. for 64 hours under a gentle stream of N2. After cooling, the reaction mixture was partitioned between water and hexanes. The organic layer was separated, washed with water (2×) and brine, then dried over anhydrous MgSO4 and evaporated to afford the crude product as an oil. The oil was dissolved in MeOH and was then treated with 2 equivalents of conc. HCl. The solvent was removed in vacuo, and the residue was then treated with diethyl ether. The resulting solids were removed by filtration. The ethereal filtrate was concentrated in vacuo and triturated with hexane to afford 380 mg (41%) of TMPH hydrochloride. It was recrystallized from boiling ethyl acetate/hexane to afford short colorless needles, mp 113-115° C. FAB-HRMS: calculated (C16H32NO2): 270.2433 found: 270.2435. After cooling the reaction mixture was partitioned between water and hexanes The organic layer was separated washed with water (2×) and brine dried over anhydrous MgSO4 evaporated to afford the crude product as an oil The solvent was removed in vacuo the residue was then treated with diethyl ether The resulting solids were removed by filtration The ethereal filtrate was concentrated in vacuo triturated with hexane

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

Procedure: In accordance with the process of Example 17, potassium t-butoxide, (336 mg; 3 m mol), n-hexyl mercaptan (354 mg; 3 m mol) and 2-oxo-bicyclo 3.1.0!hexane-1-carboxylic acid methyl ester (463 mg; 3 m mol) were used to obtain 500 mg of 5-hexylthiomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester.

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

Procedure: In accordance with the process of Example 16, potassium t-butoxide (336 mg; 3 m mol), benzyl mercaptan (372 mg; 3 m mol) and 2-oxo-bicyclo 3.1.0! hexane-1-carboxylic acid methyl ester (463 mg; 3 m mol) were used in the reaction, and the reaction product was purified by a silica gel column chromatography with ethyl acetate and n-hexane (1.5; 8.5) to obtain 650 mg of 5-benzylthiomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester as an oil. the reaction product was purified by a silica gel column chromatography with ethyl acetate and n-hexane (1.5; 8.5)

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

Procedure: In accordance with the process of Example 16, potassium t-butoxide (336 mg; 3 m mol), benzyl mercaptan (372 mg; 3 m mol) and 2-oxo-bicyclo 3.1.0! hexane-1-carboxylic acid methyl ester (463 mg; 3 m mol) were used in the reaction, and the reaction product was purified by a silica gel column chromatography with ethyl acetate and n-hexane (1.5; 8.5) to obtain 650 mg of 5-benzylthiomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester as an oil. the reaction product was purified by a silica gel column chromatography with ethyl acetate and n-hexane (1.5; 8.5)

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

Procedure: TMPH synthesis. To a mixture of 2,2,6,6-tetramethyl-4-piperidinol (472 mg, 3.0 mmol) and methyl heptanoate (476 mg, 3.3 mmol) in 3.0 mL of dimethyl formamide was added 250 mg of powdered potassium carbonate. The resulting mixture was heated at 145˜155° C. for 64 hours under a gentle stream of N2. After cooling, the reaction mixture was partitioned between water and hexanes. The organic layer was separated, washed with water (2×) and brine, then dried over anhydrous MgSO4 and evaporated to afford the crude product as an oil. The oil was dissolved in MeOH and was then treated with 2 equivalents of conc. HCl. The solvent was removed in vacuo, and the residue was then treated with diethyl ether. The resulting solids were removed by filtration. The ethereal filtrate was concentrated in vacuo and triturated with hexane to afford 380 mg (41%) of TMPH hydrochloride. It was recrystallized from boiling ethyl acetate/hexane to afford short colorless needles, mp 113-115° C. FAB-HRMS: calculated (C16H32NO2): 270.2433 found: 270.2435. After cooling the reaction mixture was partitioned between water and hexanes The organic layer was separated washed with water (2×) and brine dried over anhydrous MgSO4 evaporated to afford the crude product as an oil The solvent was removed in vacuo the residue was then treated with diethyl ether The resulting solids were removed by filtration The ethereal filtrate was concentrated in vacuo triturated with hexane

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

Procedure: TMPH synthesis. To a mixture of 2,2,6,6-tetramethyl-4-piperidinol (472 mg, 3.0 mmol) and methyl heptanoate (476 mg, 3.3 mmol) in 3.0 mL of dimethyl formamide was added 250 mg of powdered potassium carbonate. The resulting mixture was heated at 145˜155° C. for 64 hours under a gentle stream of N2. After cooling, the reaction mixture was partitioned between water and hexanes. The organic layer was separated, washed with water (2×) and brine, then dried over anhydrous MgSO4 and evaporated to afford the crude product as an oil. The oil was dissolved in MeOH and was then treated with 2 equivalents of conc. HCl. The solvent was removed in vacuo, and the residue was then treated with diethyl ether. The resulting solids were removed by filtration. The ethereal filtrate was concentrated in vacuo and triturated with hexane to afford 380 mg (41%) of TMPH hydrochloride. It was recrystallized from boiling ethyl acetate/hexane to afford short colorless needles, mp 113-115° C. FAB-HRMS: calculated (C16H32NO2): 270.2433 found: 270.2435. After cooling the reaction mixture was partitioned between water and hexanes The organic layer was separated washed with water (2×) and brine dried over anhydrous MgSO4 evaporated to afford the crude product as an oil The solvent was removed in vacuo the residue was then treated with diethyl ether The resulting solids were removed by filtration The ethereal filtrate was concentrated in vacuo triturated with hexane

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

Procedure: In analogy to the procedure described in example 10 c], [rac]-2-(4-hydroxy-2-methyl-benzyl)-heptanoic acid methyl ester (example 126 c]) was reacted with [rac]-cyclopropyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-methanol (example 121 a]) in the presence of tributylphosphine and N,N,N′,N′-tetramethyl azodicarboxamide to yield 2-(4-cyclopropyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-methoxy}-2-methyl-benzyl)-heptanoic acid methyl ester as a mixture of two diastereomeric racemates as yellow oil.

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

Procedure: In analogy to the procedure described in example 10 c], [rac]-2-(4-hydroxy-2-methyl-benzyl)-heptanoic acid methyl ester (example 126 c]) was reacted with [rac]-cyclopropyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-methanol (example 121 a]) in the presence of tributylphosphine and N,N,N′,N′-tetramethyl azodicarboxamide to yield 2-(4-cyclopropyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-methoxy}-2-methyl-benzyl)-heptanoic acid methyl ester as a mixture of two diastereomeric racemates as yellow oil.