Toluene → HCID 21959584, compound

To a stirred solution of methyl 2-methyl-2-(4-nitrophenyl)propionate (5.32 g, 23.8 mmol) in THF (200 mL) at 0° C. was added a solution of 1M BH3 in THF (25.8 mL, 45.8 mmol). The reaction was stirred at RT overnight and was quenched with MeOH. THF was evaporated under reduced pressure and the residue was diluted in EtOAc and aqueous HCl (1M) was added. The mixture was extracted with EtOAc, the organic layer was dried over MgSO4 and evaporated under reduced pressure. Purification by flash chromatography using 40% EtOAc-hexane gave a yellow solid. To the yellow solid (2.08 g, 10.8 mmol) at 0° C. in CH2Cl2 was added NMO (1.9 g, 16.1 mmol), molecular sieves 4 Å and TPAP (76 mg, 0.2 mmol). The reaction was stirred for 1 h and filtered on a silica pad. Solvent was evaporated under reduced pressure, forming the crude aldehyde which was used as is. To a suspension of methoxymethyltriphenylphosphonium chloride (6.4 g, 18.6 mmol) in THF (150 mL) was added a solution of KHMDS 0.5 M in toluene (37 mL, 18.5 mmol). The mixture was stirred for 30 min and crude aldehyde was added. The reaction was stirred at RT for 1 h and quenched with H2O. The mixture was extracted with EtOAc, dried and evaporated under reduced pressure. Et2O was added and a precipitate formed, which was filtered on a silica pad and rinsed with 40% EtOAc-hexane. The solvent was removed and crude material was dissolved in CH2Cl2. A solution of TFA-H2O (1:1, 10 mL) was added and the reaction was stirred for 2 h at RT. Aqueous NaHCO3 was added until pH 7 and the mixture was extracted with CH2Cl2. The organic layer was dried, filtered and evaporated. Crude compound was purified by flash chromatography (40% EtOAc-hexane) to give the title compound as a yellow oil.

1. customwas quenched with MeOH
2. customTHF was evaporated under reduced pressure
3. additionthe residue was diluted in EtOAc
4. additionaqueous HCl (1M) was added
5. extractionThe mixture was extracted with EtOAc
6. dry with materialthe organic layer was dried over MgSO4
7. customevaporated under reduced pressure
8. customPurification by flash chromatography
9. customgave a yellow solid
10. stirringThe reaction was stirred for 1 h
11. filtrationfiltered on a silica pad
12. customSolvent was evaporated under reduced pressure
13. customforming the crude aldehyde which
14. stirringThe mixture was stirred for 30 min
15. stirringThe reaction was stirred at RT for 1 h
16. customquenched with H2O
17. extractionThe mixture was extracted with EtOAc
18. customdried
19. customevaporated under reduced pressure
20. additionEt2O was added
21. customa precipitate formed
22. filtrationwhich was filtered on a silica pad
23. washrinsed with 40% EtOAc-hexane
24. customThe solvent was removed
25. dissolutioncrude material was dissolved in CH2Cl2
26. additionA solution of TFA-H2O (1:1, 10 mL) was added
27. stirringthe reaction was stirred for 2 h at RT
28. additionAqueous NaHCO3 was added until pH 7
29. extractionthe mixture was extracted with CH2Cl2
30. customThe organic layer was dried
31. filtrationfiltered
32. customevaporated
33. customCrude compound was purified by flash chromatography (40% EtOAc-hexane)

ORD record

ord-57c2355b5cbb4a678ab02504ff6f66cd

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08247430B2