Reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]1)=[O:4].[CH3:18][Si](C)(C)N[Si](C)(C)C.[Na].IC>C1COCC1>[CH3:1][O:2][C:3]([C:5]1([CH3:18])[CH2:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]1)=[O:4]Participants
Procedure
To a −78° C. stirred solution of Intermediate 53 (2.22 g, 9.13 mmol) in dry THF (30 ml) was added NaHMDS (sodium hexamethyldisilazane) (1.0 M in THF, 10.03 mmol) dropwise. The reaction was stirred at this temperature for 30 minutes and then iodomethane (0.682 ml, 10.95 mmol) was added dropwise. The reaction was allowed to warm to room temperature overnight with good stirring. The reaction was cooled and then quenched with saturated NH4Cl. The layers were separated and the aqueous layer was extracted three times with 20 ml of EtOAc and the organic extracts were combined. The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure. The oil was purified by silica chromatography using hexanes/EtOAc (0>15%) to yield 2.25 g (95.8%) of 3-methyl-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (Intermediate 54). 1H NMR (400 MHz, CDCl3) δ ppm 1.0 (s, 3 H), 1.3 (s, 9 H), 1.4 (m, 2 H), 1.9 (m, 2 H), 3.0 (d, J=13.2 Hz, 1 H), 3.1 (m, 1 H), 3.3 (m, 1 H), 3.5 (s, 3 H), 3.7 (d, J=13.4 Hz, 1 H).
Workup
- temperatureThe reaction was cooled
- customquenched with saturated NH4Cl
- customThe layers were separated
- extractionthe aqueous layer was extracted three times with 20 ml of EtOAc
- dry with materialThe organic phase was dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe oil was purified by silica chromatography
Sources & evidence
- ORD record
- ord-55e63d1fe9dc4a74a644d049dde20e98
- Source dataset
- uspto-grants-2008_09
- Patent number
- US07423054B2
Linked notes
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