(2S)-2-pyrrolidin-1-ylpropan-1-ol

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

Procedure: Potassium carbonate (41.4 g, 0.30 moles) was added to a solution of (S)-(+)-2-amino-1-propanol (11.27 g, 0.15 moles, Aldrich) in anhydrous acetonitrile (1.5 L) then 1,4-dibromobutane (17.9 mL, 0.15 moles, Aldrich) was added. The resulting mixture was refluxed for 24 hours then cooled to room temperature and filtered. The filtrate was concentrated under vacuum to a straw-colored solid which was dissolved in dichloromethane (150 mL) and again concentrated under vacuum to afford a straw-colored solid. This crude material, believed to be a mixture of the hydrobromide salt and the free base of the product, was again dissolved in dichloromethane (200 mL). Solid potassium carbonate and the mixture was stirred vigorously for 3 hours then filtered and concentrated under vacuum to afford a straw-colored solid. This solid, believed to still be partially the hydrobromide salt, was partitioned between dichloromethane (150 mL) and saturated aqueous potassium carbonate (50 mL). The layers (upper layer organic, lower layer aqueous) were separated and the aqueous layer was extracted with dichloromethane (2×100 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated to an amber oil. This crude product was purified by short-path vacuum distillation to afford the title compound as a colorless liquid (bp 53–54.5° C. at 1.5 mm Hg). NMR: (CDCl3, 600 MHz) δ 3.59 & 3.36 (2H, 2 dd, J=4, 10 Hz, H1), 2.64–2.72 (1H, m, H2), 2.54–2.62 (4H, m, H2′ & H5′), 1.72–1.80 (4H, m, H3′ & H4′),1.04 (3H, d, J=7 Hz, H3); MS (electrospray): m/e 130 (M+H), 112 (M−OH). [α]D+0.9° The resulting mixture was refluxed for 24 hours filtered The filtrate was concentrated under vacuum to a straw-colored solid which was dissolved in dichloromethane (150 mL) again concentrated under vacuum to afford a straw-colored solid then filtered concentrated under vacuum to afford a straw-colored solid was partitioned between dichloromethane (150 mL) and saturated aqueous potassium carbonate (50 mL) The layers (upper layer organic, lower layer aqueous) were separated the aqueous layer was extracted with dichloromethane (2×100 mL) The combined organic layers were dried over magnesium sulfate filtered evaporated to an amber oil This crude product was purified by short-path vacuum distillation

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

Procedure: A mixture of (S)-2-aminopropan-1-ol (566 mg, 7.54 mmol), 1,4-dibromobutane, and potassium carbonate (2.09 g, 15.1 mmol) in acetonitrile (70 mL) was heated at reflux overnight and allowed to cool to room temperature. The insoluble solid was filtered off, and the filtrate was concentrated under reduced pressure. The residue was diluted with DCM (75 mL) and washed (25 mL sat'd K2CO3). The aqueous phase was extracted with DCM (2×25 mL) and the combined organic extracts were dried over Na2SO4. The solvent was removed under reduced pressure and purified on a silica gel column to yield (S)-2-(pyrrolidin-1-yl)propan-1-ol (630 mg, 65%) as a clear oil. 1H NMR (CDCl3): δ 3.63 (m, 1H), 3.38 (m, 1H), 2.97 (br s, 1H), 2.69 (m, 1H), 2.60 (br s, 4H), 1.72 (br s, 4H), 1.06 (d, 3H). was heated at reflux overnight The insoluble solid was filtered off the filtrate was concentrated under reduced pressure The residue was diluted with DCM (75 mL) washed (25 mL sat'd K2CO3) The aqueous phase was extracted with DCM (2×25 mL) the combined organic extracts were dried over Na2SO4 The solvent was removed under reduced pressure purified on a silica gel column

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

Procedure: A mixture of (S)-2-aminopropan-1-ol (566 mg, 7.54 mmol), 1,4-dibromobutane, and potassium carbonate (2.09 g, 15.1 mmol) in acetonitrile (70 mL) was heated at reflux overnight and allowed to cool to room temperature. The insoluble solid was filtered off, and the filtrate was concentrated under reduced pressure. The residue was diluted with DCM (75 mL) and washed (25 mL sat'd K2CO3). The aqueous phase was extracted with DCM (2×25 mL) and the combined organic extracts were dried over Na2SO4. The solvent was removed under reduced pressure and purified on a silica gel column to yield (S)-2-(pyrrolidin-1-yl)propan-1-ol (630 mg, 65%) as a clear oil. 1H NMR (CDCl3): δ 3.63 (m, 1H), 3.38 (m, 1H), 2.97 (br s, 1H), 2.69 (m, 1H), 2.60 (br s, 4H), 1.72 (br s, 4H), 1.06 (d, 3H). was heated at reflux overnight The insoluble solid was filtered off the filtrate was concentrated under reduced pressure The residue was diluted with DCM (75 mL) washed (25 mL sat'd K2CO3) The aqueous phase was extracted with DCM (2×25 mL) the combined organic extracts were dried over Na2SO4 The solvent was removed under reduced pressure purified on a silica gel column

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

Procedure: Potassium carbonate (41.4 g, 0.30 moles) was added to a solution of (S)-(+)-2-amino-1-propanol (11.27 g, 0.15 moles, Aldrich) in anhydrous acetonitrile (1.5 L) then 1,4-dibromobutane (17.9 mL, 0.15 moles, Aldrich) was added. The resulting mixture was refluxed for 24 hours then cooled to room temperature and filtered. The filtrate was concentrated under vacuum to a straw-colored solid which was dissolved in dichloromethane (150 mL) and again concentrated under vacuum to afford a straw-colored solid. This crude material, believed to be a mixture of the hydrobromide salt and the free base of the product, was again dissolved in dichloromethane (200 mL). Solid potassium carbonate and the mixture was stirred vigorously for 3 hours then filtered and concentrated under vacuum to afford a straw-colored solid. This solid, believed to still be partially the hydrobromide salt, was partitioned between dichloromethane (150 mL) and saturated aqueous potassium carbonate (50 mL). The layers (upper layer organic, lower layer aqueous) were separated and the aqueous layer was extracted with dichloromethane (2×100 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated to an amber oil. This crude product was purified by short-path vacuum distillation to afford the title compound as a colorless liquid (bp 53–54.5° C. at 1.5 mm Hg). NMR: (CDCl3, 600 MHz) δ 3.59 & 3.36 (2H, 2 dd, J=4, 10 Hz, H1), 2.64–2.72 (1H, m, H2), 2.54–2.62 (4H, m, H2′ & H5′), 1.72–1.80 (4H, m, H3′ & H4′),1.04 (3H, d, J=7 Hz, H3); MS (electrospray): m/e 130 (M+H), 112 (M−OH). [α]D+0.9° The resulting mixture was refluxed for 24 hours filtered The filtrate was concentrated under vacuum to a straw-colored solid which was dissolved in dichloromethane (150 mL) again concentrated under vacuum to afford a straw-colored solid then filtered concentrated under vacuum to afford a straw-colored solid was partitioned between dichloromethane (150 mL) and saturated aqueous potassium carbonate (50 mL) The layers (upper layer organic, lower layer aqueous) were separated the aqueous layer was extracted with dichloromethane (2×100 mL) The combined organic layers were dried over magnesium sulfate filtered evaporated to an amber oil This crude product was purified by short-path vacuum distillation