Sodium Hydroxide → tert-Butyl 4-(hydroxymethyl)-4-(pyridin-4-yl)piperidine-1-carboxylate

HRID 391458Notes

Reaction equation

HRID 391458 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2([C:20](OCC)=[O:21])[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.C(#N)C.C(=O)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCCC1.C(OCC)(=O)C.O>[OH:21][CH2:20][C:7]1([C:4]2[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=2)[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:18])([CH3:19])[CH3:17])=[O:14])[CH2:11][CH2:12]1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 24436Sodium SulfateHCID 21226445Aluminium lithium hydrideHCID 589936931-tert-Butyl 4-ethyl 4-(pyridin-4-yl)piperidine-1,4-dicarboxylateHCID 86587134Acetonitrile dry ice

Product 1

HCID 58993619tert-Butyl 4-(hydroxymethyl)-4-(pyridin-4-yl)piperidine-1-carboxylateYield 41.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A flask was charged with 1-tert-butyl 4-ethyl 4-(pyridin-4-yl)piperidine-1,4-dicarboxylate (250 mg, 0.748 mmol) in tetrahydrofuran (3 mL) and cooled to −50° C. (acetonitrile/dry ice). Lithium aluminum hydride (0.785 ml, 1.570 mmol) was added dropwise, and the reaction was allowed to stir for 30 min. The flask was then warmed to room temperature and slowly diluted with ethyl acetate (5 mL). Water (61 μL) was added and the reaction allowed to stir for 5 min. Sodium Hydroxide (1 N in water, 120 μL) was then added and the reaction allowed to stir for 5 min. An additional portion of water (61 μL) and a small amount of sodium sulfate was added and the resulting mixture allowed to stir for 5 min. The suspension was filtered through celite, and the resulting pad washed with hot ethyl acetate. The filtrate was concentrated in vacuo to yield 90 mg (41%) of desired product. Mass Spec.: 294.05 (MH)+. LC tr=1.79 min (HPLC Method 1).

Workup

  1. stirringto stir for 5 min
  2. stirringto stir for 5 min
  3. stirringto stir for 5 min
  4. filtrationThe suspension was filtered through celite
  5. washthe resulting pad washed with hot ethyl acetate
  6. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-83e02f72e1c848f9930a7c27687a9ab5
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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