Aluminium lithium hydride → tert-butyl 2-(hydroxymethyl)-4-((tetrahydro-2H-pyran-2-yl)oxy)piperidine-1-carboxylate

HRID 2179410Notes

Reaction equation

HRID 2179410 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:10]([C:21](OC)=[O:22])[CH2:9]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[OH:22][CH2:21][CH:10]1[CH2:9][CH:8]([O:7][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)[CH2:13][CH2:12][N:11]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 681099661-tert-butyl 2-methyl 4-((tetrahydro-2H-pyran-2-yl)oxy)piperidine-1,2-dicarboxylate

Product 1

HCID 68109259tert-butyl 2-(hydroxymethyl)-4-((tetrahydro-2H-pyran-2-yl)oxy)piperidine-1-carboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of the product of step E (5.0 g, 14.6 mmol) in tetrahydrofuran (50 mL) at −20° C. was added lithium aluminum hydride (1.14 g, 30 mmol). After stirring at −20° C. for 1 h, the reaction was quenched by slow addition of water (10 mL). The resulting suspension was filtered through Celite and the filtrate concentrated in vacuo to dryness. Water (60 mL) was added and the aqueous phase was extracted with ethyl acetate (3×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification by flash column chromatography (SiO2, 4:1 to 7:3, hexanes/ethyl acetate) afforded tert-butyl 2-(hydroxymethyl)-4-((tetrahydro-2H-pyran-2-yl)oxy)piperidine-1-carboxylate (4.1 g, 81%) as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 4.73-4.63 (m, 1H), 4.44-4.23 (m, 1H), 4.02-4.00 (m, 1H), 3.90-3.70 (m, 4H), 3.50-3.48 (m, 1H), 3.21-2.42 (m, 1H), 2.09-1.93 (m, 1H), 1.82-1.71 (m, 5H), 1.54 (br s, 5H), 1.47 (s, 9H).

Workup

  1. customthe reaction was quenched by slow addition of water (10 mL)
  2. filtrationThe resulting suspension was filtered through Celite
  3. concentrationthe filtrate concentrated in vacuo to dryness
  4. additionWater (60 mL) was added
  5. extractionthe aqueous phase was extracted with ethyl acetate (3×30 mL)
  6. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash column chromatography (SiO2, 4:1 to 7:3, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-610c03a1b56d4b63ad5f6776aefe67d4
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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