Propanal → tert-Butyl 4-(3-hydroxy-1-oxopent-1-yl)-4-methoxypiperidine-1-carboxylate

HRID 8756

Reaction equation

HRID 8756 reaction equation
[C:1]([C:4]1([O:17][CH3:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].C(NC(C)C)(C)C.[Li].[CH:27](=[O:30])[CH2:28][CH3:29].[Cl-].[NH4+]>O1CCCC1>[OH:30][CH:27]([CH2:28][CH3:29])[CH2:2][C:1]([C:4]1([O:17][CH3:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[CH2:6][CH2:5]1)=[O:3]

Participants

6

Reactant 4

HCID 527PropanalHCID 25517Ammonium ChlorideHCID 21983927Tert-butyl 4-acetyl-4-methoxypiperidine-1-carboxylateHCID 45051747Lithium diisopropylamine

Product 1

HCID 21984004tert-Butyl 4-(3-hydroxy-1-oxopent-1-yl)-4-methoxypiperidine-1-carboxylateYield 55.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-acetyl-4-methoxypiperidine-1-carboxylate (0.589 g, 2.29 mmol) from Step A in tetrahydrofuran (20 mL) at −78° C. was added lithium diisopropylamine (0.650 mL, 0.974 mmol) followed by propionaldehyde (0.266 g, 0.330 mL, 4.58 mmol). After 5 min, the reaction mixture was poured into saturated ammonium chloride, and extracted three times with diethyl ether. The organic layers were combined, washed with saturated sodium chloride solution, dried over sodium sulfite, filtered, and concentrated. The residue was purified by flash chromatography eluting with 40% ethyl acetate/hexanes to afford the title compound (0.404 g). MS/EI (acetonitrile/water): m/z 216.1 (M+1−BOC) retention time=2.69 min.

Workup

  1. extractionextracted three times with diethyl ether
  2. washwashed with saturated sodium chloride solution
  3. dry with materialdried over sodium sulfite
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography
  7. washeluting with 40% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b89820f3efd14138aa3a6cb136df92cc
Source dataset
uspto-grants-2006_08
Patent number
US07091211B2

Linked notes

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