methoxymethanol

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: NMR Method for hydrocarboxylation product sample analysis. DCl/D2O/propionic acid stock solution preparation: D2O (99.99%, CIL) (74.606 g), 35% DCl in D2O (CIL) (47.755 g) and propionic acid (JT Baker) (2.198 g) were thoroughly mixed in a bottle to give 0.01765 g of propionic acid per g of stock solution. Hydrocarboxylation product sample preparation for 1H NMR analysis: About 50 mg of hydrocarboxylation sample was transferred to a 2 dram screw top vial with a phenolic cap with a polypropylene liner and the exact mass of the sample was recorded. Then 0.8288 g of stock solution was added and the mixture was heated in a heat block for 1 hour at 60° C. The vial was allowed to cool to room temperature and then the solution was transferred to an NMR tube. 1H NMR analysis: 1H NMR was recorded using 30 seconds pulse delay, 90 degree pulse angle, 16 scans and D2O lock solvent. The spectrum was referenced to the CH3 triplet of propionic acid (1.15 ppm). The meq/g concentrations of the following components were obtained from peak integrations (A1 δ 8.36 ppm, F0 δ 4.99, 4.94 ppm, MeOCH2OH δ 4.83 ppm, MGH δ 3.52 ppm, MG δ 3.84 ppm, MGM δ 3.85 ppm, G1 δ 4.35 ppm, MeOH δ 3.47 ppm, MeOPr (methyl propionate) δ 3.76 ppm, HOPr (ISTD) δ 2.50 ppm). Hydrocarboxylation product sample preparation for 1H NMR analysis Then 0.8288 g of stock solution was added to cool to room temperature the solution was transferred to an NMR tube pulse delay, 90 degree pulse angle, 16 scans and D2O

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

Procedure: To a suspension of tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate (0.1 g, 0.4 mmol) in benzene (5 mL) was added 2-methoxyethanol (0.09 ml, 1 mmol) and tri-n-butylphosphine (0.1 ml, 0.6 mmol). The resulting mixture was cooled to 0° C. followed by adding 1,1′-(azodicarbonyl)dipiperidine (0.1 g, 0.6 mmol). After 10 min, ice bath was removed; the reaction mixture was warmed up to rt. After 2 h, TLC showed there still existed 50% starting material. More methoxymethanol (2 eq, 0.06 mL) was added. The reaction mixture was continued to stir for 20 h. Hexane was added to the reaction mixture and dihydro-ADDP separated out was filtered off. The filtrate was concentrated. The crude product was purified using SiO2 chromatography (TELEDYNE ISCO REDISEP®, P/N 68-2203-027, 40 g SiO2, hexane:acetone=85%:15%, Flow=40 mL/min) to afford the desired product as colorless liquid. MS m/z: 318.4 (M+H). Calc'd. for C18H23NO4−317.38. ice bath was removed the reaction mixture was warmed up to rt After 2 h separated out was filtered off The filtrate was concentrated The crude product was purified

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

Procedure: To a suspension of tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate (0.1 g, 0.4 mmol) in benzene (5 mL) was added 2-methoxyethanol (0.09 ml, 1 mmol) and tri-n-butylphosphine (0.1 ml, 0.6 mmol). The resulting mixture was cooled to 0° C. followed by adding 1.1′-(azodicarbonyl)dipiperidine (0.1 g, 0.6 mmol). After 10 min, ice bath was removed; the reaction mixture was warmed up to rt. After 2 h, TLC showed there still existed 50% starting material. More methoxymethanol (2 eq, 0.06 mL) was added. The reaction mixture was continued to stir for 20 h. Hexane was added to the reaction mixture and dihydro-ADDP separated out was filtered off. The filtrate was concentrated. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep®, P/N 68-2203-027, 40 g SiO2, hexane:acetone=85%:15%, Flow=40 mL/min) to afford the desired product as colorless liquid. MS m/z: 318.4 (M+H). Calc'd. for C18H23NO4—317.38. ice bath was removed the reaction mixture was warmed up to rt After 2 h separated out was filtered off The filtrate was concentrated The crude product was purified

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

Procedure: To a suspension of tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate (0.1 g, 0.4 mmol) in benzene (5 mL) was added 2-methoxyethanol (0.09 ml, 1 mmol) and tri-n-butylphosphine (0.1 ml, 0.6 mmol). The resulting mixture was cooled to 0° C. followed by adding 1,1′-(azodicarbonyl)dipiperidine (0.1 g, 0.6 mmol). After 10 min, ice bath was removed; the reaction mixture was warmed up to rt. After 2 h, TLC showed there still existed 50% starting material. More methoxymethanol (2 eq, 0.06 mL) was added. The reaction mixture was continued to stir for 20 h. Hexane was added to the reaction mixture and dihydro-ADDP separated out was filtered off. The filtrate was concentrated. The crude product was purified using SiO2 chromatography (TELEDYNE ISCO REDISEP®, P/N 68-2203-027, 40 g SiO2, hexane:acetone=85%:15%, Flow=40 mL/min) to afford the desired product as colorless liquid. MS m/z: 318.4 (M+H). Calc'd. for C18H23NO4−317.38. ice bath was removed the reaction mixture was warmed up to rt After 2 h separated out was filtered off The filtrate was concentrated The crude product was purified

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

Procedure: To a suspension of tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate (0.1 g, 0.4 mmol) in benzene (5 mL) was added 2-methoxyethanol (0.09 ml, 1 mmol) and tri-n-butylphosphine (0.1 ml, 0.6 mmol). The resulting mixture was cooled to 0° C. followed by adding 1.1′-(azodicarbonyl)dipiperidine (0.1 g, 0.6 mmol). After 10 min, ice bath was removed; the reaction mixture was warmed up to rt. After 2 h, TLC showed there still existed 50% starting material. More methoxymethanol (2 eq, 0.06 mL) was added. The reaction mixture was continued to stir for 20 h. Hexane was added to the reaction mixture and dihydro-ADDP separated out was filtered off. The filtrate was concentrated. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep®, P/N 68-2203-027, 40 g SiO2, hexane:acetone=85%:15%, Flow=40 mL/min) to afford the desired product as colorless liquid. MS m/z: 318.4 (M+H). Calc'd. for C18H23NO4—317.38. ice bath was removed the reaction mixture was warmed up to rt After 2 h separated out was filtered off The filtrate was concentrated The crude product was purified

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

Procedure: To a suspension of tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate (0.1 g, 0.4 mmol) in benzene (5 mL) was added 2-methoxyethanol (0.09 ml, 1 mmol) and tri-n-butylphosphine (0.1 ml, 0.6 mmol). The resulting mixture was cooled to 0° C. followed by adding 1,1′-(azodicarbonyl)dipiperidine (0.1 g, 0.6 mmol). After 10 min, ice bath was removed; the reaction mixture was warmed up to rt. After 2 h, TLC showed there still existed 50% starting material. More methoxymethanol (2 eq, 0.06 mL) was added. The reaction mixture was continued to stir for 20 h. Hexane was added to the reaction mixture and dihydro-ADDP separated out was filtered off. The filtrate was concentrated. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep®, PIN 68-2203-027, 40 g SiO2, hexane:acetone=85%:15%, Flow=40 mL/min) to afford the desired product as colorless liquid. MS m/z: 318.4 (M+H). Calc'd. for C18H23NO4—317.38. ice bath was removed the reaction mixture was warmed up to rt After 2 h separated out was filtered off The filtrate was concentrated The crude product was purified

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

Procedure: To a suspension of tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate (0.1 g, 0.4 mmol) in benzene (5 mL) was added 2-methoxyethanol (0.09 ml, 1 mmol) and tri-n-butylphosphine (0.1 ml, 0.6 mmol). The resulting mixture was cooled to 0° C. followed by adding 1.1′-(azodicarbonyl)dipiperidine (0.1 g; 0.6 mmol). After 10 min, ice bath was removed; the reaction mixture was warmed up to rt. After 2 h, TLC showed there still existed 50% starting material. More methoxymethanol (2 eq, 0.06 mL) was added. The reaction mixture was continued to stir for 20 h. Hexane was added to the reaction mixture and dihydro-ADDP separated out was filtered off. The filtrate was concentrated. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep®, P/N 68-2203-027, 40 g SiO2, hexane:acetone=85%:15%, Flow=40 mL/min) to afford the desired product as colorless liquid. MS m/z: 318.4 (M+H). Calc'd. for C18H23NO4−317.38. ice bath was removed the reaction mixture was warmed up to rt After 2 h separated out was filtered off The filtrate was concentrated The crude product was purified

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

Procedure: To a suspension of tert-butyl 2-(3-hydroxyquinolin-6-yl)acetate (0.1 g, 0.4 mmol) in benzene (5 mL) was added 2-methoxyethanol (0.09 ml, 1 mmol) and tri-n-butylphosphine (0.1 ml, 0.6 mmol). The resulting mixture was cooled to 0° C. followed by adding 1.1′-(azodicarbonyl)dipiperidine (0.1 g, 0.6 mmol). After 10 min, ice bath was removed; the reaction mixture was warmed up to rt. After 2 h, TLC showed there still existed 50% starting material. More methoxymethanol (2 eq, 0.06 mL) was added. The reaction mixture was continued to stir for 20 h. Hexane was added to the reaction mixture and dihydro-ADDP separated out was filtered off. The filtrate was concentrated. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep®, P/N 68-2203-027, 40 g SiO2, hexane:acetone=85%:15%, Flow=40 mL/min) to afford the desired product as colorless liquid. MS m/z: 318.4 (M+H). Calc'd. for C18H23NO4—317.38. ice bath was removed the reaction mixture was warmed up to rt After 2 h separated out was filtered off The filtrate was concentrated The crude product was purified

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: NMR Method for hydrocarboxylation product sample analysis. DCl/D2O/propionic acid stock solution preparation: D2O (99.99%, CIL) (74.606 g), 35% DCl in D2O (CIL) (47.755 g) and propionic acid (JT Baker) (2.198 g) were thoroughly mixed in a bottle to give 0.01765 g of propionic acid per g of stock solution. Hydrocarboxylation product sample preparation for 1H NMR analysis: About 50 mg of hydrocarboxylation sample was transferred to a 2 dram screw top vial with a phenolic cap with a polypropylene liner and the exact mass of the sample was recorded. Then 0.8288 g of stock solution was added and the mixture was heated in a heat block for 1 hour at 60° C. The vial was allowed to cool to room temperature and then the solution was transferred to an NMR tube. 1H NMR analysis: 1H NMR was recorded using 30 seconds pulse delay, 90 degree pulse angle, 16 scans and D2O lock solvent. The spectrum was referenced to the CH3 triplet of propionic acid (1.15 ppm). The meq/g concentrations of the following components were obtained from peak integrations (A1 δ 8.36 ppm, F0 δ 4.99, 4.94 ppm, MeOCH2OH δ 4.83 ppm, MGH δ 3.52 ppm, MG δ 3.84 ppm, MGM δ 3.85 ppm, G1 δ 4.35 ppm, MeOH δ 3.47 ppm, MeOPr (methyl propionate) δ 3.76 ppm, HOPr (ISTD) δ 2.50 ppm). Hydrocarboxylation product sample preparation for 1H NMR analysis Then 0.8288 g of stock solution was added to cool to room temperature the solution was transferred to an NMR tube pulse delay, 90 degree pulse angle, 16 scans and D2O