2-(N-methylanilino)ethanol

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

Procedure: A solution of 74.0 g (0.489 mol) of N-(2-hydroxyethyl)-N-methylaniline in 100 mL of pyridine was treated dropwise with 55 g (0.54 mol) of acetic anhydride. The resulting mixture was heated at reflux for 10 hr, then cooled and poured onto 500 g of ice. The mixture was extracted three times with dichloromethane (3×100 mL), the combined extracts were dried using magnesium sulfate (MgSO4) and the solvent was evaporated. The residue was distilled at reduced pressure, producing 84.2 g of a slightly yellow oil, b.p. 107°-116° C. (0.4 mm). The resulting mixture was heated at reflux for 10 hr cooled The mixture was extracted three times with dichloromethane (3×100 mL) the combined extracts were dried the solvent was evaporated The residue was distilled at reduced pressure producing 84.2 g of a slightly yellow oil, b.p. 107°-116° C. (0.4 mm)

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

Procedure: In a mixture of compound 2a (1.25 g, 8.3 mmol) and CH2Cl2 (50 mL), SOCl2 (1.2 mls, 16.5 mmol) was added dropwise over 20 min. During addition the solution turned from colorless to yellow. After the addition was complete, the mixture was heated to reflux for one hour. After cooling to room temperature, the mixture was quenched carefully with cold, saturated aqueous K2CO3 (50 mL). The mixture was then extracted with CH2Cl2, and the combined organic layer was washed with brine and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc to provide the compound 2b (0.55 g, 3.2 mmol, 39.3% yield) as a yellow oil. HRMS (ESI, positive) m/z calcd. for C9H13ClN [M+H]+: 170.07310, found: 170.07309. 1H NMR (400 MHz, Chloroform-d) δ 7.24 (dd, J=8.8, 7.3 Hz, 2H), 6.73 (m, J=14.2, 7.6 Hz, 3H), 3.71-3.56 (m, 4H), 3.00 (s, 3H). was added dropwise over 20 min During addition the solution After the addition the mixture was heated to reflux for one hour the mixture was quenched carefully with cold, saturated aqueous K2CO3 (50 mL) The mixture was then extracted with CH2Cl2 the combined organic layer was washed with brine dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with hexane/EtOAc

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

Procedure: In a mixture of compound 2a (1.25 g, 8.3 mmol) and CH2Cl2 (50 mL), SOCl2 (1.2 mls, 16.5 mmol) was added dropwise over 20 min. During addition the solution turned from colorless to yellow. After the addition was complete, the mixture was heated to reflux for one hour. After cooling to room temperature, the mixture was quenched carefully with cold, saturated aqueous K2CO3 (50 mL). The mixture was then extracted with CH2Cl2, and the combined organic layer was washed with brine and dried over Na2SO4. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc to provide the compound 2b (0.55 g, 3.2 mmol, 39.3% yield) as a yellow oil. HRMS (ESI, positive) m/z calcd. for C9H13ClN [M+H]+: 170.07310, found: 170.07309. 1H NMR (400 MHz, Chloroform-d) δ 7.24 (dd, J=8.8, 7.3 Hz, 2H), 6.73 (m, J=14.2, 7.6 Hz, 3H), 3.71-3.56 (m, 4H), 3.00 (s, 3H). was added dropwise over 20 min During addition the solution After the addition the mixture was heated to reflux for one hour the mixture was quenched carefully with cold, saturated aqueous K2CO3 (50 mL) The mixture was then extracted with CH2Cl2 the combined organic layer was washed with brine dried over Na2SO4 The solvent was evaporated the residue was purified by silica gel column chromatography with hexane/EtOAc

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

Procedure: N-methylaniline (5 mls, 0.05 mol) was reacted with 2-Iodoethanol (3.599 mls, 0.05 mol) and diisopropylethylamine (8.039 mls, 0.05 mol) in ACN at 70° C. for 16 hours. The solvent was evaporated and the residue was purified by silica gel column chromatography with hexane/EtOAc to provide the compound as a yellow orange oil, 2a (4.48 g, 0.03 mol, 64.5% yield). 1H NMR (400 MHz, Chloroform-d) δ 7.27-7.15 (m, 2H), 6.81-6.67 (m, 3H), 3.74 (t, J=5.8 Hz, 2H), 3.42 (t, J=5.8 Hz, 2H), 2.92 (s, 3H). The solvent was evaporated the residue was purified by silica gel column chromatography with hexane/EtOAc

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

Procedure: A 1 L flask was charged with 2-(N-methylanilino)ethanol (8) (151.3 g, 1 mole), methylene chloride (250 mL), and triethylamine (151 g, 1.48 mole). Acetic anhydride (153.35 g, 1.5 mole) was added to the solution at room temperature through an addition funnel. The product (7) was collected by vacuum distillation (122 g, bp 110° C. at 400 micron Hg). The product (7) was collected by vacuum distillation (122 g, bp 110° C. at 400 micron Hg)

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

Procedure: A 1 L flask was charged with 2-(N-methylanilino)ethanol (8) (151.3 g, 1 mole), methylene chloride (250 mL), and triethylamine (151 g, 1.48 mole). Acetic anhydride (153.35 g, 1.5 mole) was added to the solution at room temperature through an addition funnel. The product (7) was collected by vacuum distillation (122 g, bp 110° C. at 400 micron Hg). The product (7) was collected by vacuum distillation (122 g, bp 110° C. at 400 micron Hg)