Diethyl Ether → tert-butyl (2S)-2-formylpyrrolidine-1-carboxylate
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C@H:9]1[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.CCOCC.C([O-])(O)=O.[Na+]>C(Cl)Cl.CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C@H:9]1[CH:10]=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]Participants
Conditions
- Temperature
- 0 °C
Procedure
To a stirred solution of tert-butyloxycarbonyl-L-prolinol (3.50 g, 17.41 mmol) in DCM (25 mL) at 0° C. was added triethylamine (9.7 mL, 60.93 mmol), followed by sulfur trioxide-pyridine complex (8.30 g, 6.96 mmol) in DMSO (10 mL). The reaction mixture was stirred at 0° C. for 1 h. Hexanes (20 mL), Et2O (10 mL) and aqueous sat. NaHCO3 (30 mL) were added and the layers separated. The aqueous layer was extracted with a mixture of hexanes (20 mL) and Et2O (10 mL) twice. The combined organic layers were washed with 1M aqueous NaH2PO4 (30 mL), then brine (30 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification by column chromatography (SiO2, 20% EtOAc/hexanes) gave the title compound (2.70 g, 77%) as a colourless oil. δH (DMSO-d6), mixture of rotamers: 9.49-9.36 (1H, m), 4.14-4.02 (1H, m), 3.45-3.26 (2H, m), 2.14-2.00 (1H, m), 1.96-1.69 (3H, m), 1.42 and 1.34 (9H, s, rotameric).
Workup
- customthe layers separated
- extractionThe aqueous layer was extracted with a mixture of hexanes (20 mL) and Et2O (10 mL) twice
- washThe combined organic layers were washed with 1M aqueous NaH2PO4 (30 mL)
- dry with materialbrine (30 mL), dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customPurification by column chromatography (SiO2, 20% EtOAc/hexanes)
Sources & evidence
- ORD record
- ord-b3119a425f734da3bc2389972e2ae6ff
- Source dataset
- uspto-grants-2012_12
- Patent number
- US08324204B2
Reaction notes
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