Aluminium lithium hydride → Tert-butyl 3-(hydroxymethyl)-3-methylpiperidine-1-carboxylate
Reaction equation
C[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.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[C:14]([O:13][C:11]([N:7]1[CH2:8][CH2:9][CH2:10][C:5]([CH2:3][OH:2])([CH3:18])[CH2:6]1)=[O:12])([CH3:17])([CH3:16])[CH3:15]Participants
Procedure
To a 0° C. stirred solution of Intermediate 54 (1.17 g, 4.56 mmol) in dry THF (20 ml) was added LiAlH4 (1.0 M in THF, 9.11 ml, 9.11 mmol) dropwise and the reaction was allowed to warm to room temperature. Upon completion as indicated by TLC, the reaction was carefully quenched with saturated NH4Cl and EtOAc was added. The layers were separated, the aqueous layer was extracted with EtOAc (3×15 ml) and the organic extracts were combined. The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure to yield 0.844 g (42.1%) of 3-hydroxymethyl-3-methyl-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 55). 1H NMR (400 MHz, CDCl3) δ ppm 0.9 (s, 3 H), 1.3 (m, 2 H), 1.5 (s, 9 H), 1.5 (m, 3 H), 2.9 (s, 1 H), 3.1 (s, 1 H), 3.5 (d, J=11.5 Hz, 1 H), 3.8 (m, 2 H).
Workup
- customthe reaction was carefully quenched with saturated NH4Cl and EtOAc
- additionwas added
- customThe layers were separated
- extractionthe aqueous layer was extracted with EtOAc (3×15 ml)
- dry with materialThe organic phase was dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-bc31d8fe807a44c381d87c55603b1a6d
- Source dataset
- uspto-grants-2008_09
- Patent number
- US07423054B2
Reaction notes
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