Tetrahydrofuran → Tert-butyl 4,4-bis(hydroxymethyl)piperidine-1-carboxylate

HRID 1013490Notes

Reaction equation

HRID 1013490 reaction equation
[N:1]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:6][CH2:5][C:4]([C:12](OCC)=[O:13])([C:7](OCC)=[O:8])[CH2:3][CH2:2]1.C1COCC1.[Li+].[BH4-]>C1(C)C=CC=CC=1>[OH:8][CH2:7][C:4]1([CH2:12][OH:13])[CH2:5][CH2:6][N:1]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 4148881Lithium borohydrideHCID 579258841-tert-Butyl 4,4-diethyl piperidine-1,4,4-tricarboxylate

Product 1

HCID 21955203Tert-butyl 4,4-bis(hydroxymethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-tert-butyl 4,4-diethyl piperidine-1,4,4-tricarboxylate (2.00 g, 6.07 mmol) in 1:1 THF:toluene (50 mL) was added LiBH4 (15.18 mL, 30.4 mmol, 2.0 M in THF). The reaction was stirred at 60° C. for 18 h. It was then quenched with saturated NH4Cl and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), and evaporated. The residue was purified by flash chromatography (15-100% EtOAc/hexanes) to give tert-butyl 4,4-bis(hydroxymethyl)piperidine-1-carboxylate as a colorless solid. 1H NMR (CDCl3, 600 MHz) δ 3.66 (d, J=5.0 Hz, 4H), 3.41-3.37 (m, 4H), 2.29 (t, J=5.1 Hz, 2H), 1.47-1.45 (m, 4H), 1.45 (s, 9H). MS: cal'd 268 (MNa+), exp 268 (MNa+).

Workup

  1. customIt was then quenched with saturated NH4Cl
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by flash chromatography (15-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e3174916fee547dd8a52117ccb75e1e3
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

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