Methane → HCID 58092758, compound

Trimethylaluminum in toluene (2 M, 15.95 mmol) was added dropwise to a mixture of NH4Cl (15.95 mmol) in toluene (2 mL) at 0° C. with the formation of methane gas. The reaction mixture was allowed to warm to rt, stirred for a further 15 min and then slowly treated with a solution of (2S,3S)-3-azidomethyl-1-((S)-1-phenyl-ethyl)-pyrrolidine-2-carboxylic acid methyl ester (Stage 36.4) (7.98 mmol) in toluene (8 mL). Additional reagent prepared from NH4Cl (15.95 mmol) in toluene (2 mL) and trimethylaluminum in toluene (2 M, 15.95 mmol) at 0° C. was added after 18 h. After stirring for 44 h, the mixture was cooled to 0° C., quenched with 1M HCl and then washed with CH2Cl2 (3×). The aqueous phase was basified with a 1:1 saturated solution of NaHCO3/saturated solution of Rochelle's salt and extracted with THF (10×). The combined organic layers were dried (Na2SO4), filtered and concentrated. The residue was purified using a RediSep® silica gel column to afford the title compound as a yellow oil. HPLC: tR=2.50 min (method G); ESI-MS: [M+H]+ 274; TLC: Rf=0.26 (3:1 Hex/EtOAc).

1. additionwas added after 18 h
2. stirringAfter stirring for 44 h
3. temperaturethe mixture was cooled to 0° C.
4. customquenched with 1M HCl
5. washwashed with CH2Cl2 (3×)
6. extractionextracted with THF (10×)
7. dry with materialThe combined organic layers were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified

ORD record

ord-be8dffe9c89b435cbcce129cee95793f

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08357707B2