3-Hydroxybenzaldehyde → tert-Butyl 4-(3-formylphenoxy)piperidine-1-carboxylate

HRID 2359413Notes

Reaction equation

HRID 2359413 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].O[CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.C([O-])(O)=O.[Na+]>C1COCC1>[CH:5]([C:4]1[CH:3]=[C:2]([CH:9]=[CH:8][CH:7]=1)[O:1][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1)=[O:6]

Participants

7

Reactant 5

HCID 1013-HydroxybenzaldehydeHCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 53439173tert-Butyl 4-(3-formylphenoxy)piperidine-1-carboxylateYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 3-hydroxybenzaldehyde (1.0 g), tert-butyl 4-hydroxypiperidine-1-carboxylate (1.67 g, 1.1 eq), triphenylphosphine (2.35 g, 1.1 eq) in THF (15 mL) at 0° C. was added dropwise DEAD (6.74 g, 4.75 eq). The mixture was warmed to room temperature and stirred for 2 days. To the reaction mixture was added saturated NaHCO3 (aq), and the aqueous layer was extracted with ethyl acetate (15 mL×3), the organic layers were combined, dried (Na2SO4), and purified on silica gel column chromatography (10% ethyl acetate in pentane) to obtain the desired product as a light yellow oil (900 mg, 38% yield).

Workup

  1. extractionthe aqueous layer was extracted with ethyl acetate (15 mL×3)
  2. dry with materialdried (Na2SO4)
  3. custompurified on silica gel column chromatography (10% ethyl acetate in pentane)

Sources & evidence

ORD record
ord-30eb74f1ecce4c229a45820831382195
Source dataset
uspto-grants-2014_04
Patent number
US08685970B2

Reaction notes

Loading…