1-[2-(dibenzylamino)ethyl]cyclopropan-1-ol

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

Procedure: Treat a 0° C. solution of 1-(2-(dibenzylamino)ethyl)cyclopropanol (3 g, 10.6 mmol) in THF (50 mL), under N2, portion wise with NaH (60%, 0.85 g, 21.3 mmol), stir at 0° C. for 0.5 h, add iodomethane (1.82 g, 12.8 mmol) drop wise, warm to RT and stir for 3 h. Cool the mixture to 0° C., quench with satd. NH4Cl and partially concentrate. Extract with EtOAc (3×), wash the combined organics with brine, dry over Na2SO4, concentrate and purify via silica gel chromatography to afford the title compound (1.2 g, 38%). 1H NMR (400 MHz, CDCl3): δ 7.39-7.21 (m, 10H), 3.60 (s, 4H), 3.12 (s, 3H), 2.65 (t, J=8 Hz, 2H), 1.75 (t, J=8 Hz, 2H), 0.68-0.65 (m, 2H), 0.34-0.31 (m, 2H). Cool the mixture to 0° C. quench with satd NH4Cl and partially concentrate Extract with EtOAc (3×) wash the combined organics with brine dry over Na2SO4 concentrate purify via silica gel chromatography

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

Procedure: Treat a 0° C. solution of 1-(2-(dibenzylamino)ethyl)cyclopropanol (3 g, 10.6 mmol) in THF (50 mL), under N2, portion wise with NaH (60%, 0.85 g, 21.3 mmol), stir at 0° C. for 0.5 h, add iodomethane (1.82 g, 12.8 mmol) drop wise, warm to RT and stir for 3 h. Cool the mixture to 0° C., quench with satd. NH4Cl and partially concentrate. Extract with EtOAc (3×), wash the combined organics with brine, dry over Na2SO4, concentrate and purify via silica gel chromatography to afford the title compound (1.2 g, 38%). 1H NMR (400 MHz, CDCl3): δ 7.39-7.21 (m, 10H), 3.60 (s, 4H), 3.12 (s, 3H), 2.65 (t, J=8 Hz, 2H), 1.75 (t, J=8 Hz, 2H), 0.68-0.65 (m, 2H), 0.34-0.31 (m, 2H). Cool the mixture to 0° C. quench with satd NH4Cl and partially concentrate Extract with EtOAc (3×) wash the combined organics with brine dry over Na2SO4 concentrate purify via silica gel chromatography

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

Procedure: Add titanium isopropoxide (860 mg, 3.03 mmol) to a solution of ethyl 3-(dibenzylamino)propanoate (9.0 g, 30.3 mmol) in ethyl ether, cool to 0° C., add ethyl magnesium bromide (3M in Et2O, 30.3 mL) drop-wise over 1 h, maintaining the temperature at ˜0-4° C., allow to warm to RT and stir overnight. Cool to 0° C., add satd. NH4Cl, stir at RT for 15 minutes, make basic with satd. NaHCO3 and extract with EtOAc (2×). Wash the combined organics with brine, dry over MgSO4, concentrate and purify via silica gel chromatography to give the title compound (7.5 g, 88%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.20-7.15 (m, 8H), 7.12-7.07 (m, 2H), 3.45 (s, 4H), 2.61-2.59 (m, 2H), 1.57 (t, J=5.6 Hz, 2H), 0.36-0.33 (m, 2H), 0.30-0.17 (m, 2H). maintaining the temperature at ˜0-4° C. to warm to RT Cool to 0° C. add NaHCO3 and extract with EtOAc (2×) Wash the combined organics with brine dry over MgSO4 concentrate purify via silica gel chromatography

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

Procedure: A 0° C. solution of 1-(2-(dibenzylamino)ethyl)cyclopropanol (3 g, 10.6 mmol) in THF (50 mL), under N2, was treated portion-wise with NaH (60%, 0.85 g, 21.3 mmol), stirred at 0° C. for 0.5 h, treated drop-wise with MeI (1.82 g, 12.8 mmol), warmed to RT and stirred for 3 h. The mixture was cooled to 0° C., quenched with satd. NH4Cl and partially concentrated. The residue was extracted with EtOAc (3×) and the combined organics were washed with brine, dried over Na2SO4, concentrated and purified via silica gel chromatography to afford N,N-dibenzyl-2-(1-methoxycyclopropyl)ethanamine (1.2 g, 38%). 1H NMR (400 MHz, CDCl3): δ 7.39-7.21 (m, 10 H), 3.60 (s, 4 H), 3.12 (s, 3 H), 2.65 (t, J=8 Hz, 2 H), 1.75 (t, J=8 Hz, 2 H), 0.68-0.65 (m, 2 H), 0.34-0.31 (m, 2 H). warmed to RT stirred for 3 h The mixture was cooled to 0° C. quenched with satd NH4Cl and partially concentrated The residue was extracted with EtOAc (3×) the combined organics were washed with brine dried over Na2SO4 concentrated purified via silica gel chromatography

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

Procedure: Titanium isopropoxide (860 mg, 3.03 mmol) was added to a solution of ethyl 3-(dibenzylamino)propanoate (9.0 g, 30.3 mmol) in Et2O, cooled to 0° C., treated drop-wise with ethyl magnesium bromide (3M in Et2O, 30.3 mL) over 1 h, maintaining the temperature at 0˜4° C., then allowed to warm to RT and stirred overnight. The mixture was cooled to 0° C., treated with satd. NH4Cl, stirred at RT for 15 minutes, made basic with satd. NaHCO3 and extracted with EtoAc (2×). The combined organics were washed with brine, dried over MgSO4, concentrated and purified via silica gel chromatograph to give 1-(2-(dibenzylamino)ethyl)cyclopropanol (7.5 g, 88%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.20-7.15 (m, 8 H), 7.12-7.07 (m, 2 H), 3.45 (s, 4 H), 2.61-2.59 (m, 2 H), 1.57 (t, J=5.6 Hz, 2 H), 0.36-0.33 (m, 2 H), 0.30-0.17 (m, 2 H). maintaining the temperature at 0˜4° C. to warm to RT The mixture was cooled to 0° C. treated with satd NaHCO3 and extracted with EtoAc (2×) The combined organics were washed with brine dried over MgSO4 concentrated purified via silica gel chromatograph

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

Procedure: Titanium isopropoxide (860 mg, 3.03 mmol) was added to a solution of ethyl 3-(dibenzylamino)propanoate (9.0 g, 30.3 mmol) in Et2O, cooled to 0° C., treated drop-wise with ethyl magnesium bromide (3M in Et2O, 30.3 mL) over 1 h, maintaining the temperature at 0˜4° C., then allowed to warm to RT and stirred overnight. The mixture was cooled to 0° C., treated with satd. NH4Cl, stirred at RT for 15 minutes, made basic with satd. NaHCO3 and extracted with EtoAc (2×). The combined organics were washed with brine, dried over MgSO4, concentrated and purified via silica gel chromatograph to give 1-(2-(dibenzylamino)ethyl)cyclopropanol (7.5 g, 88%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.20-7.15 (m, 8 H), 7.12-7.07 (m, 2 H), 3.45 (s, 4 H), 2.61-2.59 (m, 2 H), 1.57 (t, J=5.6 Hz, 2 H), 0.36-0.33 (m, 2 H), 0.30-0.17 (m, 2 H). maintaining the temperature at 0˜4° C. to warm to RT The mixture was cooled to 0° C. treated with satd NaHCO3 and extracted with EtoAc (2×) The combined organics were washed with brine dried over MgSO4 concentrated purified via silica gel chromatograph

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

Procedure: Titanium isopropoxide (860 mg, 3.03 mmol) was added to a solution of ethyl 3-(dibenzylamino)propanoate (9.0 g, 30.3 mmol) in Et2O, cooled to 0° C., treated drop-wise with ethyl magnesium bromide (3M in Et2O, 30.3 mL) over 1 h, maintaining the temperature at 0˜4° C., then allowed to warm to RT and stirred overnight. The mixture was cooled to 0° C., treated with satd. NH4Cl, stirred at RT for 15 minutes, made basic with satd. NaHCO3 and extracted with EtoAc (2×). The combined organics were washed with brine, dried over MgSO4, concentrated and purified via silica gel chromatograph to give 1-(2-(dibenzylamino)ethyl)cyclopropanol (7.5 g, 88%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.20-7.15 (m, 8 H), 7.12-7.07 (m, 2 H), 3.45 (s, 4 H), 2.61-2.59 (m, 2 H), 1.57 (t, J=5.6 Hz, 2 H), 0.36-0.33 (m, 2 H), 0.30-0.17 (m, 2 H). maintaining the temperature at 0˜4° C. to warm to RT The mixture was cooled to 0° C. treated with satd NaHCO3 and extracted with EtoAc (2×) The combined organics were washed with brine dried over MgSO4 concentrated purified via silica gel chromatograph

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

Procedure: Treat a 0° C. solution of 1-(2-(dibenzylamino)ethyl)cyclopropanol (3 g, 10.6 mmol) in THF (50 mL), under N2, portion wise with NaH (60%, 0.85 g, 21.3 mmol), stir at 0° C. for 0.5 h, add iodomethane (1.82 g, 12.8 mmol) drop wise, warm to RT and stir for 3 h. Cool the mixture to 0° C., quench with satd. NH4Cl and partially concentrate. Extract with EtOAc (3×), wash the combined organics with brine, dry over Na2SO4, concentrate and purify via silica gel chromatography to afford the title compound (1.2 g, 38%). 1H NMR (400 MHz, CDCl3): δ 7.39-7.21 (m, 10H), 3.60 (s, 4H), 3.12 (s, 3H), 2.65 (t, J=8 Hz, 2H), 1.75 (t, J=8 Hz, 2H), 0.68-0.65 (m, 2H), 0.34-0.31 (m, 2H). Cool the mixture to 0° C. quench with satd NH4Cl and partially concentrate Extract with EtOAc (3×) wash the combined organics with brine dry over Na2SO4 concentrate purify via silica gel chromatography

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

Procedure: Add titanium isopropoxide (860 mg, 3.03 mmol) to a solution of ethyl 3-(dibenzylamino)propanoate (9.0 g, 30.3 mmol) in ethyl ether, cool to 0° C., add ethyl magnesium bromide (3M in Et2O, 30.3 mL) drop-wise over 1 h, maintaining the temperature at ˜0-4° C., allow to warm to RT and stir overnight. Cool to 0° C., add satd. NH4Cl, stir at RT for 15 minutes, make basic with satd. NaHCO3 and extract with EtOAc (2×). Wash the combined organics with brine, dry over MgSO4, concentrate and purify via silica gel chromatography to give the title compound (7.5 g, 88%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.20-7.15 (m, 8H), 7.12-7.07 (m, 2H), 3.45 (s, 4H), 2.61-2.59 (m, 2H), 1.57 (t, J=5.6 Hz, 2H), 0.36-0.33 (m, 2H), 0.30-0.17 (m, 2H). maintaining the temperature at ˜0-4° C. to warm to RT Cool to 0° C. add NaHCO3 and extract with EtOAc (2×) Wash the combined organics with brine dry over MgSO4 concentrate purify via silica gel chromatography