Diisobutylaluminum hydride → N-(1-(4-(hydroxymethyl)phenyl)piperidin-4-yl)acetamide

HRID 591609Notes

Reaction equation

HRID 591609 reaction equation
[C:1]([NH:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:21]=[CH:20][C:14]([C:15](OCC)=[O:16])=[CH:13][CH:12]=2)[CH2:7][CH2:6]1)(=[O:3])[CH3:2].CC(C[AlH]CC(C)C)C>C(Cl)Cl>[OH:16][CH2:15][C:14]1[CH:13]=[CH:12][C:11]([N:8]2[CH2:7][CH2:6][CH:5]([NH:4][C:1](=[O:3])[CH3:2])[CH2:10][CH2:9]2)=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 66670978Ethyl 4-(4-acetamidopiperidin-1-yl)benzoate

Product 1

HCID 66745026N-(1-(4-(hydroxymethyl)phenyl)piperidin-4-yl)acetamideYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of ethyl 4-(4-acetamidopiperidin-1-yl)benzoate (0.123 g, 0.42 mmol) in CH2Cl2 (10 mL) under nitrogen at −78° C. was treated with DIBAL-H (1.0M in hexanes, 0.950 mL, 0.95 mmol) dropwise, via a syringe. After 20 minutes, the mixture was warmed to room temperature, stirred for 1 hour, and quenched with 10% Rochelle's salt. After stirring for 10 minutes, CH2Cl2 (50 mL) was added, and the stirring was continued for 15 additional minutes. The layers were separated and the aqueous phase was extracted with CH2Cl2 (50 mL) and ethyl acetate (50 mL). The combined organic phases were dried (MgSO4), filtered, concentrated, and purified by flash chromatography on silica gel, eluting with 100% ethyl acetate to 10% MeOH/ethyl acetate to afford N-(1-(4-(hydroxymethyl)phenyl)piperidin-4-yl)acetamide as a white solid (0.025 g, 24%).

Workup

  1. customquenched with 10% Rochelle's salt
  2. stirringAfter stirring for 10 minutes
  3. additionCH2Cl2 (50 mL) was added
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with CH2Cl2 (50 mL) and ethyl acetate (50 mL)
  6. dry with materialThe combined organic phases were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by flash chromatography on silica gel
  10. washeluting with 100% ethyl acetate to 10% MeOH/ethyl acetate

Sources & evidence

ORD record
ord-a560f34ba5584bc1ac49f83144a939f1
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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