1-phenylpropan-2-ol

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

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

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 4 liter three-necked flask fitted with a mechanical stirrer and a reflux condenser, were placed 1500 ml of water, 150 g of sodium hydroxide (pellets), 190 ml of ethanol and 180 g of phenylacetone. The mixture was stirred and heated to 80° C., and 150 g of Raney alloy was added very cautiously by small amounts over about 1 hour. During the addition, heating was discontinued and the temperature was maintained at 85°-87° C. In a 4 liter three-necked flask fitted with a mechanical stirrer and a reflux condenser 150 g of Raney alloy was added very cautiously by small amounts over about 1 hour During the addition heating the temperature was maintained at 85°-87° C.

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

Procedure: This half-ester R-3c (250 mg; 1.0 mmol) was dissolved in methanol (2 mL) and treated with potassium carbonate (276 mg; 2.0 mmol; 2 equiv.) and stirred overnight to completely consume 3c (tlc analysis). The reaction mixture was diluted with water (25 mL) and extracted with ether (3×10 mL). The combined extracts were dried (MgSO4) and concentrated to afford 118 mg (79%) of R-1c. All achiral properties of 1c are as reported above. The absolute configuration of 1c was not exhaustively proven, but was presumed to be R-(-) by analogy with the enzymatic results of 1a and 1b. 1H nmr analysis of the MTPA ester using an analogous procedure to that of Dale et al., J. Org. Chem., 1969, 34, 2543, indicated 54% ee for R-1c. [α]D20 -8.2° (c. 1.19, CH3OH). to completely consume 3c (tlc analysis) The reaction mixture was diluted with water (25 mL) extracted with ether (3×10 mL) The combined extracts were dried (MgSO4) concentrated to afford 118 mg (79%) of R-1c

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

Procedure: 3-Bromo-6-nitrofuro[3,2-c]pyridin-7-ol (Intermediate 10) was reacted with racemic 1-phenylpropan-2-ol following the procedure described for Intermediate 8. The resulting intermediate was reacted with iron/HCl as described in Example 2 to give the title compound. MS (ES+): m/z 347.22/349.23 (100/99) [MH+]. HPLC: tR=0.81 min (HPLC-ACQUITY, Analytical). 1H NMR (400 MHz, CD3OD): δ=1.32 (d, J=6.1 Hz, 3H), 2.93 (dd, J=13.5, 6.2 Hz, 1H), 3.10 (dd, J=13.6, 6.6 Hz, 1H), 4.98 (m, 1H), 7.13-7.21 (m, 1H), 7.25 (d, J=4.3 Hz, 4H), 7.70 (s, 1H), 7.82 (s, 1H).

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

Procedure: 3-Bromo-6-nitrofuro[3,2-c]pyridin-7-ol (Intermediate 10) was reacted with racemic 1-phenylpropan-2-ol following the procedure described for Intermediate 8. The resulting intermediate was reacted with iron/HCl as described in Example 2 to give the title compound. MS (ES+): m/z 347.22/349.23 (100/99) [MH+]. HPLC: tR=0.81 min (HPLC-ACQUITY, Analytical). 1H NMR (400 MHz, CD3OD): δ=1.32 (d, J=6.1 Hz, 3H), 2.93 (dd, J=13.5, 6.2 Hz, 1H), 3.10 (dd, J=13.6, 6.6 Hz, 1H), 4.98 (m, 1H), 7.13-7.21 (m, 1H), 7.25 (d, J=4.3 Hz, 4H), 7.70 (s, 1H), 7.82 (s, 1H).

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

Procedure: A solution of 1-phenylpropan-2-ol (2.72 g, 20 mmol) in CH2Cl2 (20 mL) was added pyridinium chlorochromate (PCC, 5.4 g, 25 mmol) at 0° C. and the mixture was stirred for 3 h. The mixture was concentrated and purified by flash column chromatography (PE/EtOAc=20:1) to give the title compound (2.3 g, 84%) as a yellow oil. The mixture was concentrated purified by flash column chromatography (PE/EtOAc=20:1)

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

Procedure: A solution of 1-phenylpropan-2-ol (2.72 g, 20 mmol) in CH2Cl2 (20 mL) was added pyridinium chlorochromate (PCC, 5.4 g, 25 mmol) at 0° C. and the mixture was stirred for 3 h. The mixture was concentrated and purified by flash column chromatography (PE/EtOAc=20:1) to give the title compound (2.3 g, 84%) as a yellow oil. The mixture was concentrated purified by flash column chromatography (PE/EtOAc=20:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1-phenyl-2-propanol (2.18 g, 16.0 mmol) in CH2Cl2 (100 mL) is added Dess-Martin periodinane (50 mL, 15 wt % solution in methylene chloride) at 0° C. After stirring at 0° C. for 1 h, the mixture is warmed to RT and stirred for 1.5 h. To the reaction mixture is added saturated NaHCO3 (200 mL) and stirred at RT for 20 min. The mixture is filtered through Celite and the organic phase is washed with water and brine then dried over MgSO4. The solvent is removed under reduced pressure and the crude material is purified by flash chromatography to afford the title compound as a colorless oil: (M+1)+=135. the mixture is warmed to RT stirred for 1.5 h stirred at RT for 20 min The mixture is filtered through Celite the organic phase is washed with water and brine then dried over MgSO4 The solvent is removed under reduced pressure the crude material is purified by flash chromatography

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

Procedure: A solution of 1-phenylpropan-2-ol (2.72 g, 20 mmol) in CH2Cl2 (20 mL) was added pyridinium chlorochromate (PCC, 5.4 g, 25 mmol) at 0° C. and the mixture was stirred for 3 h. The mixture was concentrated and purified by flash column chromatography (PE/EtOAc=20:1) to give the title compound (2.3 g, 84%) as a yellow oil. The mixture was concentrated purified by flash column chromatography (PE/EtOAc=20:1)

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

Procedure: A solution of 1-phenylpropan-2-ol (2.72 g, 20 mmol) in CH2Cl2 (20 mL) was added pyridinium chlorochromate (PCC, 5.4 g, 25 mmol) at 0° C. and the mixture was stirred for 3 h. The mixture was concentrated and purified by flash column chromatography (PE/EtOAc=20:1) to give the title compound (2.3 g, 84%) as a yellow oil. The mixture was concentrated purified by flash column chromatography (PE/EtOAc=20:1)