tert-butyl N-[4-(2-hydroxyethyl)phenyl]carbamate

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

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

Procedure: 4-(2-Hydroxyethyl)phenylcarbamic acid tert-butyl ester (1.03 g; 4.34 mmole) and 2-ethoxy-3-(4-hydroxyphenyl)propanoic acid ethyl ester (1.03 g; 4.34 mmole) were dissolved in dichloromethane under argon at room temperature. Azodicarbonyl dipiperidine (1.65 g, 6.5 mmole) and thereafter triphenylphosphine (1.37 g; 5.2 mmole) were added. After stirring at room temperature for 6 hours the solvent was evaporated in vacuo. Purification by chromatography on silica gel using heptane ethyl acetate (2:1) as eluant gave 1.78 g (yield 89%) of 3-{4-[2-(4-tert-butoxycarbonylaminophenyl)ethoxy]-phenyl}-2-ethoxypropanoic acid ethyl ester. was evaporated in vacuo Purification by chromatography on silica gel

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

Procedure: 4-(2-Hydroxyethyl)phenylcarbamic acid tert-butyl ester (1.03 g; 4.34 mmole) and 2-ethoxy-3-(4-hydroxyphenyl)propanoic acid ethyl ester (1.03 g; 4.34 mmole) were dissolved in dichloromethane under argon at room temperature. Azodicarbonyl dipiperidine (1.65 g, 6.5 mmole) and thereafter triphenylphosphine (1.37 g; 5.2 mmole) were added. After stirring at room temperature for 6 hours the solvent was evaporated in vacuo. Purification by chromatography on silica gel using heptane ethyl acetate (2:1) as eluant gave 1.78 g (yield 89%) of 3-{4-[2-(4-tert-butoxycarbonylaminophenyl)ethoxy]-phenyl}-2-ethoxypropanoic acid ethyl ester. was evaporated in vacuo Purification by chromatography on silica gel

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

Procedure: 3-[4-(2-{4-tert-Butoxycarbonylaminophenyl}ethoxy)phenyl]-2-(2,2,2-trifluoroethoxy)propanoic acid methyl ester was synthesized using the same method as in Example 62 (a) from 3-(4-hydroxyphenyl)-2-(2,2,2-trifluoroethoxy)propanoic acid methyl ester and 4-(2-hydroxyethyl)phenylcarbamic acid tert-butyl ester(described in Example 38b.

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

Procedure: 4-(2-Hydroxyethyl)phenylcarbamic tert-butyl ester (described in Example 38b) (170 g; 0.716 mole) was suspended in dichloromethane (1.7 l) and placed in an ice bath. Pyridine (113 g; 1.43 mole) was added giving a clear yellow solution. p-Toluenesulfonyl chloride (205 g; 1.07 mole) was dissolved in dichloromethane (850 ml) and added slowly with stirring to the reaction mixture during 45 minutes. The reaction mixture was allowed to reach room temperature over night. The solution was then washed with water (4×1 L) and dried with magnesium sulfate. The solvent was evaporated under reduced pressure until the weight was 440 g. The remaining brownish oil was slowly poured into heptane (1.6 L) with vigorous stirring. After approx. 20 seconds the oil started to crystallize. The heavy precipitate was filtered off, washed with heptane (200 ml) and dried in vacuo at 40° C. over night. This procedure gave 274 g (97.8% yield) of crude 2-[4-(tert-butoxycarbonylamino)phenyl]ethyl-4-methylbenzenesulfonate. placed in an ice bath giving a clear yellow solution added slowly to reach room temperature over night The solution was then washed with water (4×1 L) dried with magnesium sulfate The solvent was evaporated under reduced pressure until the weight The remaining brownish oil was slowly poured into heptane (1.6 L) with vigorous stirring After approx. 20 seconds the oil started to crystallize The heavy precipitate was filtered off washed with heptane (200 ml) dried in vacuo at 40° C. over night

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

Procedure: 4-(2-Hydroxyethyl)phenylcarbamic acid tert-butyl ester (1.03 g; 4.34 mmole) and 2-ethoxy-3-(4-hydroxyphenyl)propanoic acid ethyl ester (described in Example 20b) (1.03 g; 4.34 mmole) were dissolved in dichloromethane under argon at room temperature. Azodicarbonyl dipiperidine (1.65 g; 6.5 mmole) and thereafter triphenylphosphine (1.37 g; 5.2 mmole) were added. After stirring at room temperature for 6 hours the solvent was evaporated in vacuo. Purification by chromatography on silica gel using heptane:ethyl acetate (2:1) as eluant gave 1.78 g (yield 89%) of 3-{4-[2-(4-tert-butoxycarbonylaminophenyl)ethoxy]-phenyl}-2-ethoxypropanoic acid ethyl ester. was evaporated in vacuo Purification by chromatography on silica gel

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

Procedure: Compound (c) (1.03 g; 4.34 mmole) and (b) (1.03 g; 4.34 mmole) were dissolved in dichloromethane under argon at room temperature. Azodicarbonyl dipiperidine (1.65 g; 6.5 mmole) and thereafter triphenylphosphine (1.37 g; 5.2 mmole) were added. After stirring at room temperature for 6 hours the solvent was evaporated in vacuo. Purification by chromatography on silica gel using heptane:ethyl acetate (2:1) as eluant gave 1.78 g (yield 89%) of the desired product was evaporated in vacuo Purification by chromatography on silica gel

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

Procedure: Compound (c) (1.03 g; 4.34 mmole) and (b) (1.03 g; 4.34 mmole) were dissolved in dichloromethane under argon at room temperature. Azodicarbonyl dipiperidine (1.65 g; 6.5 mmole) and thereafter triphenylphosphine (1.37 g; 5.2 mmole) were added. After stirring at room temperature for 6 hours the solvent was evaporated in vacuo. Purification by chromatography on silica gel using heptane:ethyl acetate (2:1) as eluant gave 1.78 g (yield 89%) of the desired product was evaporated in vacuo Purification by chromatography on silica gel

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

Procedure: Compound (c) (1.03 g; 4.34 mmole) and (b) (1.03 g; 4.34 mmole) were dissolved in dichloromethane under argon at room temperature. Azodicarbonyl dipiperidine (1.65 g; 6.5 mmole) and thereafter triphenylphosphine (1.37 g; 5.2 mmole) were added. After stirring at room temperature for 6 hours the solvent was evaporated in vacuo. Purification by chromatography on silica gel using heptane:ethyl acetate (2:1) as eluant gave 1.78 g (yield 89%) of the desired product was evaporated in vacuo Purification by chromatography on silica gel

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

Procedure: Compound (c) (1.03 g; 4.34 mmole) and (b) (1.03 g; 4.34 mmole) were dissolved in dichloromethane under argon at room temperature. Azodicarbonyl dipiperidine (1.65 g; 6.5 mmole) and thereafter triphenylphosphine (1.37 g; 5.2 mmole) were added. After stirring at room temperature for 6 hours the solvent was evaporated in vacuo. Purification by chromatography on silica gel using heptane:ethyl acetate (2:1) as eluant gave 1.78 g (yield 89%) of the desired product. was evaporated in vacuo Purification by chromatography on silica gel

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

Procedure: A solution of 4.9 g of 1-benzyloxy-4-(2-hydroxyethyl)benzene (8) in 100 mL of dimethoxyethane (DME) and 5 drops triethylamine was heated to reflux and 1.8 mL of diketene was slowly added. The solvent was removed under reduced pressure to yield 6.4 g of 2-(benzyloxyphenyl)ethylacetoacetate (9), m.p. 54°-56° C. to reflux The solvent was removed under reduced pressure

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

Procedure: A solution of 4.9 g of 1-benzyloxy-4-(2-hydroxyethyl)benzene (8) in 100 mL of dimethoxyethane (DME) and 5 drops triethylamine was heated to reflux and 1.8 mL of diketene was slowly added. The solvent was removed under reduced pressure to yield 6.4 g of 2-(benzyloxyphenyl)ethylacetoacetate (9), m.p. 54°-56° C. to reflux The solvent was removed under reduced pressure