Water → HCID 90413919, compound

Participants

Reaction Conditions

Reaction Steps

To compound 1 (almost 120 kg) and 1590 kg DCM was added 152 kg of trityl chloride at −5 to −10° C. under nitrogen atm. in a 2000 L reactor and a solution of TEA (triethylamine) (71 kg) and DMAP (2.88 kg) in DCM 175 kg was slowly added. The reaction mixture was stirred at −5 to −10° C. for 32 hr and warmed to 15-20° C. (4° C./h) and kept at 15-20° C. for 12 h after which time LC-MS showed trityl chloride<2%. The reaction was quenched by 20 kg water, the organic phase was separated, dried and concentrated to a residue, and MTBE (methyl tert-butyl ether) (500 kg) was added, with stirring to result in a clear solution. Water (600 kg) was added, and the mixture was stirred for 3 h, then 500 kg heptane was added, cooled to −5° C.-0° C. and stirred for 3 h. A small amount of yellow solid precipitated, filtered by a centrifuge. Then the organic layer washed with saturated NH4Cl solution (600 kg), pH was adjusted with 0.5 N aqueous citric acid to pH=3-4, and the organic layer collected, dried with Na2SO4, filtered and concentrated under vacuum to get crude compound (2), (3aR,6aR)-2,2-dimethyl-6-((trityloxy)methyl)tetrahydrofuro[3,4-d][1,3]dioxol-4-ol, as oil. This crude (2) (228.5 kg) was purified by silica gel column (1.0× of silica gel was used to pre-absorb the crude material, 2.3× of silica gel was used to pack the column), eluted by the solvent (EA (ethyl acetate): PE (petroleum ether)=1:8), to get 93 kg (four batches) of (2) dispersed in toluene (assay by HPLC).

Provenance & Evidence