4-(trimethylsilyloxymethyl)aniline

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

Procedure: 7-(1-Isobutoxy-ethoxycarbamoyl)-heptanoic acid (5.0 g, 1.72 mmol, 1.0 eq) and 4-trimethylsilanyloxymethyl-phenylamine (3.38 g, 1.72 mmol, 1.0 eq) were stirred together in DMF (140 mL). To the mixture was added PyBroP (10.5 g, 2.25 mmol, 1.3 eq) and DiPEA (3.9 mL, 2.25 mmol, 1.3 eq). The reaction was stirred under a nitrogen atmosphere overnight at room temperature. Ethyl acetate (200 mL) and water (200 mL) were added. The aqueous phase was isolated and re-extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with water (2×50 mL) and brine (50 mL), then dried (MgSO4), filtered and concentrated in vacuo. The crude product was dissolved in the minimum of ethyl acetate and purified by passing through a pad of silica. The product was washed through the silica using ethyl acetate and collected in 100 mL conical flasks until elution ceased by LCMS analysis. Purification gave a yellow oil (3.59 g, 53% yield). LCMS purity 61%, m/z 417 [M++Na]+ The aqueous phase was isolated re-extracted with ethyl acetate (2×100 mL) The combined organic phases were washed with water (2×50 mL) and brine (50 mL) dried (MgSO4) filtered concentrated in vacuo The crude product was dissolved in the minimum of ethyl acetate purified The product was washed through the silica collected in 100 mL conical flasks until elution Purification

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

Procedure: 7-(1-Isobutoxy-ethoxycarbamoyl)-heptanoic acid (5.0 g, 1.72 mmol, 1.0 eq) and 4-trimethylsilanyloxymethyl-phenylamine (3.38 g, 1.72 mmol, 1.0 eq) were stirred together in DMF (140 mL). To the mixture was added PyBroP (10.5 g, 2.25 mmol, 1.3 eq) and DiPEA (3.9 mL, 2.25 mmol, 1.3 eq). The reaction was stirred under a nitrogen atmosphere overnight at room temperature. Ethyl acetate (200 mL) and water (200 mL) were added. The aqueous phase was isolated and re-extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with water (2×50 mL) and brine (50 mL), then dried (MgSO4), filtered and concentrated in vacuo. The crude product was dissolved in the minimum of ethyl acetate and purified by passing through a pad of silica. The product was washed through the silica using ethyl acetate and collected in 100 mL conical flasks until elution ceased by LCMS analysis. Purification gave a yellow oil (3.59 g, 53% yield). LCMS purity 61%, m/z 417 [M++Na]+ The aqueous phase was isolated re-extracted with ethyl acetate (2×100 mL) The combined organic phases were washed with water (2×50 mL) and brine (50 mL) dried (MgSO4) filtered concentrated in vacuo The crude product was dissolved in the minimum of ethyl acetate purified The product was washed through the silica collected in 100 mL conical flasks until elution Purification

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

Procedure: To a stirred solution of 4-amino benzyl alcohol (16.0 g, 13.0 mmol, 1.0 eq) in THF (400 mL), was added triethylamine (18.9 mL, 13.6 mmol, 1.05 eq) followed by trimethylchlorosilane (17.2 mL, 13.6 mmol, 1.05 eq). The reaction mixture was stirred under a nitrogen atmosphere overnight at room temperature. THF was evaporated under vacuum and the mixture partitioned with ethyl acetate (300 mL) and water (300 mL). The organic phase was isolated and the aqueous layer re-extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with brine (2×150 mL), dried (MgSO4), filtered and concentrated in vacuo. The product was obtained as a yellow oil (24.0 g, 95% yield) and used in stage 4 without further purification. THF was evaporated under vacuum the mixture partitioned with ethyl acetate (300 mL) and water (300 mL) The organic phase was isolated the aqueous layer re-extracted with ethyl acetate (2×100 mL) The combined organic phases were washed with brine (2×150 mL) dried (MgSO4) filtered concentrated in vacuo

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

Procedure: 7-(1-Isobutoxy-ethoxycarbamoyl)-heptanoic acid (5.0 g, 1.72 mmol, 1.0 eq) and 4-trimethylsilanyloxymethyl-phenylamine (3.38 g, 1.72 mmol, 1.0 eq) were stirred together in DMF (140 mL). To the mixture was added PyBroP (10.5 g, 2.25 mmol, 1.3 eq) and DiPEA (3.9 mL, 2.25 mmol, 1.3 eq). The reaction was stirred under a nitrogen atmosphere overnight at room temperature. Ethyl acetate (200 mL) and water (200 mL) were added. The aqueous phase was isolated and re-extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with water (2×50 mL) and brine (50 mL), then dried (MgSO4), filtered and concentrated in vacuo. The crude product was dissolved in the minimum of ethyl acetate and purified by passing through a pad of silica. The product was washed through the silica using ethyl acetate and collected in 100 mL conical flasks until elution ceased by LCMS analysis. Purification gave a yellow oil (3.59 g, 53% yield). LCMS purity 61%, m/z 417 [M++Na]+ The aqueous phase was isolated re-extracted with ethyl acetate (2×100 mL) The combined organic phases were washed with water (2×50 mL) and brine (50 mL) dried (MgSO4) filtered concentrated in vacuo The crude product was dissolved in the minimum of ethyl acetate purified The product was washed through the silica collected in 100 mL conical flasks until elution Purification

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

Procedure: To a stirred solution of 4-amino benzyl alcohol (16.0 g, 13.0 mmol, 1.0 eq) in THF (400 mL), was added triethylamine (18.9 mL, 13.6 mmol, 1.05 eq) followed by trimethylchlorosilane (17.2 mL, 13.6 mmol, 1.05 eq). The reaction mixture was stirred under a nitrogen atmosphere overnight at room temperature. THF was evaporated under vacuum and the mixture partitioned with ethyl acetate (300 mL) and water (300 mL). The organic phase was isolated and the aqueous layer re-extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with brine (2×150 mL), dried (MgSO4), filtered and concentrated in vacuo. The product was obtained as a yellow oil (24.0 g, 95% yield) and used in stage 4 without further purification. THF was evaporated under vacuum the mixture partitioned with ethyl acetate (300 mL) and water (300 mL) The organic phase was isolated the aqueous layer re-extracted with ethyl acetate (2×100 mL) The combined organic phases were washed with brine (2×150 mL) dried (MgSO4) filtered concentrated in vacuo

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

Procedure: To a stirred solution of 4-amino benzyl alcohol (16.0 g, 13.0 mmol, 1.0 eq) in THF (400 mL), was added triethylamine (18.9 mL, 13.6 mmol, 1.05 eq) followed by trimethylchlorosilane (17.2 mL, 13.6 mmol, 1.05 eq). The reaction mixture was stirred under a nitrogen atmosphere overnight at room temperature. THF was evaporated under vacuum and the mixture partitioned with ethyl acetate (300 mL) and water (300 mL). The organic phase was isolated and the aqueous layer re-extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with brine (2×150 mL), dried (MgSO4), filtered and concentrated in vacuo. The product was obtained as a yellow oil (24.0 g, 95% yield) and used in stage 4 without further purification. THF was evaporated under vacuum the mixture partitioned with ethyl acetate (300 mL) and water (300 mL) The organic phase was isolated the aqueous layer re-extracted with ethyl acetate (2×100 mL) The combined organic phases were washed with brine (2×150 mL) dried (MgSO4) filtered concentrated in vacuo

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

Procedure: 7-(1-Isobutoxy-ethoxycarbamoyl)-heptanoic acid (5.0 g, 1.72 mmol, 1.0 eq) and 4-trimethylsilanyloxymethyl-phenylamine (3.38 g, 1.72 mmol, 1.0 eq) were stirred together in DMF (140 mL). To the mixture was added PyBroP (10.5 g, 2.25 mmol, 1.3 eq) and DiPEA (3.9 mL, 2.25 mmol, 1.3 eq). The reaction was stirred under a nitrogen atmosphere overnight at room temperature. Ethyl acetate (200 mL) and water (200 mL) were added. The aqueous phase was isolated and re-extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with water (2×50 mL) and brine (50 mL), then dried (MgSO4), filtered and concentrated in vacuo. The crude product was dissolved in the minimum of ethyl acetate and purified by passing through a pad of silica. The product was washed through the silica using ethyl acetate and collected in 100 mL conical flasks until elution ceased by LCMS analysis. Purification gave a yellow oil (3.59 g, 53% yield). LCMS purity 61%, m/z 417 [M++Na]+ The aqueous phase was isolated re-extracted with ethyl acetate (2×100 mL) The combined organic phases were washed with water (2×50 mL) and brine (50 mL) dried (MgSO4) filtered concentrated in vacuo The crude product was dissolved in the minimum of ethyl acetate purified The product was washed through the silica collected in 100 mL conical flasks until elution Purification

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

Procedure: To a stirred solution of 4-amino benzyl alcohol (16.0 g, 13.0 mmol, 1.0 eq) in THF (400 mL), was added triethylamine (18.9 mL, 13.6 mmol, 1.05 eq) followed by trimethylchlorosilane (17.2 mL, 13.6 mmol, 1.05 eq). The reaction mixture was stirred under a nitrogen atmosphere overnight at room temperature. THF was evaporated under vacuum and the mixture partitioned with ethyl acetate (300 mL) and water (300 mL). The organic phase was isolated and the aqueous layer re-extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with brine (2×150 mL), dried (MgSO4), filtered and concentrated in vacuo. The product was obtained as a yellow oil (24.0 g, 95% yield) and used in stage 4 without further purification. THF was evaporated under vacuum the mixture partitioned with ethyl acetate (300 mL) and water (300 mL) The organic phase was isolated the aqueous layer re-extracted with ethyl acetate (2×100 mL) The combined organic phases were washed with brine (2×150 mL) dried (MgSO4) filtered concentrated in vacuo

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

Procedure: 7-(1-Isobutoxy-ethoxycarbamoyl)-heptanoic acid (5.0 g, 1.72 mmol, 1.0 eq) and 4-trimethylsilanyloxymethyl-phenylamine (3.38 g, 1.72 mmol, 1.0 eq) were stirred together in DMF (140 mL). To the mixture was added PyBroP (10.5 g, 2.25 mmol, 1.3 eq) and DiPEA (3.9 mL, 2.25 mmol, 1.3 eq). The reaction was stirred under a nitrogen atmosphere overnight at room temperature. Ethyl acetate (200 mL) and water (200 mL) were added. The aqueous phase was isolated and re-extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with water (2×50 mL) and brine (50 mL), then dried (MgSO4), filtered and concentrated in vacuo. The crude product was dissolved in the minimum of ethyl acetate and purified by passing through a pad of silica. The product was washed through the silica using ethyl acetate and collected in 100 mL conical flasks until elution ceased by LCMS analysis. Purification gave a yellow oil (3.59 g, 53% yield). LCMS purity 61%, m/z 417 [M++Na]+ The aqueous phase was isolated re-extracted with ethyl acetate (2×100 mL) The combined organic phases were washed with water (2×50 mL) and brine (50 mL) dried (MgSO4) filtered concentrated in vacuo The crude product was dissolved in the minimum of ethyl acetate purified The product was washed through the silica collected in 100 mL conical flasks until elution Purification

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

Procedure: To a stirred solution of 4-amino benzyl alcohol (16.0 g, 13.0 mmol, 1.0 eq) in THF (400 mL), was added triethylamine (18.9 mL, 13.6 mmol, 1.05 eq) followed by trimethylchlorosilane (17.2 mL, 13.6 mmol, 1.05 eq). The reaction mixture was stirred under a nitrogen atmosphere overnight at room temperature. THF was evaporated under vacuum and the mixture partitioned with ethyl acetate (300 mL) and water (300 mL). The organic phase was isolated and the aqueous layer re-extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with brine (2×150 mL), dried (MgSO4), filtered and concentrated in vacuo. The product was obtained as a yellow oil (24.0 g, 95% yield) and used in stage 4 without further purification. THF was evaporated under vacuum the mixture partitioned with ethyl acetate (300 mL) and water (300 mL) The organic phase was isolated the aqueous layer re-extracted with ethyl acetate (2×100 mL) The combined organic phases were washed with brine (2×150 mL) dried (MgSO4) filtered concentrated in vacuo