Triphenylphosphine → 4-[3-(1-Methyl-4-piperidinyl)propoxy]benzaldehyde

HRID 2420974Notes

Reaction equation

HRID 2420974 reaction equation
C[C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:30][N:31]1[CH2:36][CH2:35][CH:34]([CH2:37][CH2:38][CH2:39]O)[CH2:33][CH2:32]1.C(OC(N=NC(OC(C)(C)C)=O)=O)(C)(C)C>C1COCC1>[CH3:30][N:31]1[CH2:36][CH2:35][CH:34]([CH2:37][CH2:38][CH2:39][O:10][C:8]2[CH:9]=[CH:2][C:3]([CH:4]=[O:5])=[CH:6][CH:7]=2)[CH2:33][CH2:32]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 4581854-Hydroxy-2-methylbenzaldehydeHCID 155406773-(1-Methylpiperidin-4-yl)propan-1-ol

Product 1

HCID 857723684-[3-(1-Methyl-4-piperidinyl)propoxy]benzaldehydeYield 41.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cooled solution of 2-methyl-4-hydroxybenzaldehyde (722 mg, 5.3 mmol), PPh3 polymer resin (3 mmol/g, 2.2 g, 6.4 mmol), and 3-(1-methyl-piperidin-4-yl)-propan-1-ol (833 mg, 5.3 mmol, 1.0 equiv) in THF (25 mL) was added di-tert-butyl-azodicarboxylate (1.47 g, 6.4 mmol). The reaction mixture was allowed to warm to rt and was stirred for 16 h. The mixture was filtered through diatomaceous earth, diluted with water, and extracted three times with EtOAc. The combined extracts were dried (Na2SO4) and concentrated. Purification by Method 1 afforded 578 mg (40%) of the desired aldehyde. MS (ESI): mass calcd for C16H23NO2, 261.17; m/z found, 262.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 9.85 (s, 1H), 7.80 (d, J=8.6, 2H), 6.97 (d, J=8.6, 2H), 4.01 (t, J=6.4, 2H), 2.84-2.82 (m, 2H), 2.25 (s, 3H), 1.92-1.78 (m, 4H), 1.71-1.69 (m, 2H), 1.41-1.37 (m, 2H), 1.29-1.26 (m, 3H).

Workup

  1. filtrationThe mixture was filtered through diatomaceous earth
  2. additiondiluted with water
  3. extractionextracted three times with EtOAc
  4. dry with materialThe combined extracts were dried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification by Method 1

Sources & evidence

ORD record
ord-0061e8b64ab94df281f553d089459d6f
Source dataset
uspto-grants-2011_06
Patent number
US07956066B2

Reaction notes

Loading…