Lithium diisopropylamide → Methyl 3-(3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-hydroxybutanoyl)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxylate

Add a solution of LDA (2M in THF, 19.5 mL, 3.89 mmol) to a suspension of 3-acetyl-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxylate (7.4 g, 3.11 mmol) in dry THF (80 mL) at −78° C. under N2. After stirring for 1.5 h, add 1-(3,5-Dichloro-phenyl)-2,2,2-trifluoro-ethanone (9.9 g, 3.73 mmol) to the reaction mixture and stir the resultant mixture at the same temperature for additional 2 hours. Quench the reaction with saturated NH4Cl aqueous solution. Extract the aqueous mixture with EtOAc (100 mL×3). The combined organic layers are washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum. Purify the residue by silica gel chromatograph (PE:EtOAc 50:1) to afford methyl 3-(3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-hydroxybutanoyl)-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxylate as an orange solid (9.1 g, 60.4%). MS (m/z): 481 (M+1).

1. customQuench
2. customthe reaction with saturated NH4Cl aqueous solution
3. extractionExtract the aqueous mixture with EtOAc (100 mL×3)
4. washThe combined organic layers are washed with brine
5. dry with materialdried over anhydrous Na2SO4
6. concentrationconcentrated under vacuum
7. customPurify the residue by silica gel chromatograph (PE:EtOAc 50:1)

ORD 기록

ord-ed68061f728c46daa148c8fb72f80f2a

출처 데이터셋

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09255111B2