Methyl morpholine oxide → HCID 57068393, compound

To a solution of (S)-1-tert-butyl 2-methyl 1H-pyrrole-1,2(2H,5H)-dicarboxylate (1.0 g, 4.5 mmol) in dioxane —H2O (4:1) was added NMO (580 mg, 4.95 mmol) and OsO4 114 mg, 0.45 mmol, 2.5 wt % in H2O) and the reaction mixture was stirred for 24 h at r.t. Quenched with 10% aqueous Na2S2O3 solution and extracted with ethyl acetate. The combined organic layers washed with brine and dried over anhydrous Na2SO4. The resultant residue was dissolved in acetone (5 mL), added catalytic amount of PPTS and dimethoxy propane (1.5 mL). The reaction mixture was stirred over night at r.t. and diluted with ethyl acetate, washed with saturated NaHCO3 and brine. Dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was dissolved in ether (5.0 mL) and LiAlH4 (3.0 mL, 3.0 mmol, 1M solution in ether) was added at 0° C. under N2 atmosphere. Stirred for 1 h and quenched with 1N NaOH (0.1 mL) solution. Anhydrous MgSO4 was added and filtered through celite. The filtrate was concentrated under reduced pressure and purified by flash chromatography (5% MeOH—CH2Cl2) to afford (3aR,4R,6aS)-tert-butyl 4-(hydroxymethyl)-2,2-dimethyldihydro-3aH-[1,3]dioxolo[4,5-c]pyrrole-5(4H)-carboxylate (550 mg, 45%, over 3 steps). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.32 (s, 6H) 1.47 (s, 9H) 3.33-3.38 (m, 1H) 3.50 (dd, J=13.14, 6.06 Hz, 2H) 4.54 (d, J=3.79 Hz, 1H) 4.59-4.61 (m, 1H) 4.66-4.73 (m, 2H).

1. customQuenched with 10% aqueous Na2S2O3 solution
2. extractionextracted with ethyl acetate
3. washThe combined organic layers washed with brine
4. dry with materialdried over anhydrous Na2SO4
5. dissolutionThe resultant residue was dissolved in acetone (5 mL)
6. additionadded catalytic amount of PPTS and dimethoxy propane (1.5 mL)
7. stirringThe reaction mixture was stirred over night at r.t.
8. additiondiluted with ethyl acetate
9. washwashed with saturated NaHCO3 and brine
10. dry with materialDried over anhydrous Na2SO4
11. concentrationconcentrated under reduced pressure
12. dissolutionThe residue was dissolved in ether (5.0 mL)
13. stirringStirred for 1 h
14. customquenched with 1N NaOH (0.1 mL) solution
15. additionAnhydrous MgSO4 was added
16. filtrationfiltered through celite
17. concentrationThe filtrate was concentrated under reduced pressure
18. custompurified by flash chromatography (5% MeOH—CH2Cl2)

ORD record

ord-11a047100ae24312aa16a5f4d913d834

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071766B2