Dichloromethane → (R)-3-[(S)-Hydroxy(tetrahydropyran-4-yl)methyl]pyrrolidine-1-carboxylic Acid t-Butyl Ester
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([CH2:13][OH:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.[CH3:18][C:19]1(C)N([O])C(C)(C)[CH2:22][CH2:21][CH2:20]1.[O-:29]Cl.[Na+]>O.C([O-])(O)=O.[Na+].[Br-].[K+]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([C@@H:13]([OH:14])[CH:20]2[CH2:21][CH2:22][O:29][CH2:18][CH2:19]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]Participants
8
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 0 °C
Procedure
To a solution of (R)-3-hydroxymethyl-pyrrolidine-1-carboxylic acid t-butyl ester (20.0 g, 99.4 mmol) in DCM (200 mL, 3100 mmol) was added TEMPO ((310 mg, 2.0 mmol) and potassium bromide (590 mg, 5.0 mmol). This mixture was cooled at 0° C. and a 1:1 mixture of 0.7 M NaOCl in water (140 mL) and saturated aqueous NaHCO3 solution (140 ml) was added dropwise over a period of 30 minutes. The resultant mixture was extracted with DCM (200 mL). The combined organic layers were washed with water (2×200 mL) and saturated aqueous NaCl (1×200 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo to yield the title compound as an oil (15.5 g), which was used without further purification.
Workup
- additionwas added dropwise over a period of 30 minutes
- extractionThe resultant mixture was extracted with DCM (200 mL)
- washThe combined organic layers were washed with water (2×200 mL) and saturated aqueous NaCl (1×200 mL)
- dry with materialThe organic layer was dried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-2c4081020ecb4c0bbc1fb7270d66f64e
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08853255B2
Reaction notes
Loading…