1,2-Dichloroethane → Benzenepropanoyl chloride

A mixture of 2-amino-2-methyl-t-propanol (4 ml, 42 mmol), CH2Cl2 (200 mL), 4-acetyl benzoic acid (1, 6.9 g, 42 mmol), EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl, 12.1 g. 63 mmol), HOBT (N-hydroxybenzotriazole H2O, 6.4 g, 42 mmol), and Hunig's base (diisopropylethylamine, 22 mL, 126 mmol) was stirred at room temperature for 18 hours. Upon completion (TLC, LC/MS) the reaction mixture was concentrated, and the resulting residue was diluted with EtOAc (50 mL) and washed with NaHCO3 (2×40 mL) and brine (40 mL). The organic layer was dried (MgSO4), filtered, and the filtrate was concentrated. The crude material was purified by flash column chromatography (4:1:1 hexanes:EtOAc:CH2Cl2:1:1:1 hexanes:EtOAc:CH2Cl2; EtOAc:CH2Cl2) to remove bisacylated material. Alcohol 2 was obtained in 54% yield (5.36 g). Tetrapropylammonium perruthenate (TPAP, 387 mg, 1.1 mmol) was added portion-wise to a solution of 2 (5.36 g, 22.8 mmol), CH2Cl2 (46 mL, 2 mL/mmol). 4-methyl-morpholine N-oxide (4 g. 34.2 mmol), and molecular sieves, 4 Å activated powder (11.4 g, 500 mg/mmol) at 0° C. under N2. The reaction was allowed to warm to r.t. after 15 minutes. After 1 hour the reaction was complete (TLC) and was filtered through silica, which was eluted with EtOAc (100 mL), and the filtrate was concentrated. This yielded 4.4 g of light pink solid (3). The material was recrystallized: 1:1 Flexanes:EtOAc (5 mL), CH2Cl2 (20 mL), and MeOH (10 mL) were added portion-wise with heating and sonication. This was brought to a boil after which hexane (100 mL) was added while cooling. Crystals immediately began to precipitate as the solution was cooled. The mixture was filtered and the crystals were washed with hexane (10 mL), affording 2.46 g (46%) of 3 as off-white fluffy crystals.

1. concentrationUpon completion (TLC, LC/MS) the reaction mixture was concentrated
2. additionthe resulting residue was diluted with EtOAc (50 mL)
3. washwashed with NaHCO3 (2×40 mL) and brine (40 mL)
4. dry with materialThe organic layer was dried (MgSO4)
5. filtrationfiltered
6. concentrationthe filtrate was concentrated
7. customThe crude material was purified by flash column chromatography (4:1:1 hexanes:EtOAc:CH2Cl2:1:1:1 hexanes:EtOAc:CH2Cl2; EtOAc:CH2Cl2)
8. customto remove bisacylated material

ORD record

ord-561b4ff70992471d98959a1487e9908e

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07919524B2