Mesitylene → (RS)-1-(6-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol

HRID 278457Notes

Reaction equation

HRID 278457 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([CH2:13]OS(C1C=CC(C)=CC=1)(=O)=O)[CH2:7][CH2:6]2.C[CH:26]([C:33]1([OH:39])[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[C:40]1(C)C=C(C)C=C(C)C=1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([CH2:13][N:36]1[CH2:35][CH2:34][C:33]([CH2:26][C:27]3[CH:28]=[CH:29][C:30]([CH3:40])=[CH:31][CH:32]=3)([OH:39])[CH2:38][CH2:37]1)[CH2:7][CH2:6]2

Participants

4

Reactant 3

HCID 7947MesityleneHCID 11405260(RS)-Toluene-4-sulfonic acid 6-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl esterHCID 226283564-(Methyl-benzyl)-piperidin-4-ol

Product 1

HCID 22628368(RS)-1-(6-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-olYield 67.3%

Procedure

(RS)-Toluene-4-sulfonic acid 6-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl ester (1.32 g, 3.81 mmol) and 4-(methyl-benzyl)-piperidin-4-ol (3.13 g, 15.24 mmol) in mesitylene (100 ml) was heated at 140° C. for 20 hr. Following evaporation of the solvent the crude material was partioned between CH2Cl2 (50 ml) and 5% NaHCO3 (30 ml), the aqueous phase was extracted with CH2Cl2 (2×100 ml) washed with satd. NaCl solution (50 ml), dried (Na2SO4), filtered and evaporated. The crude product was chomatographed over SiO2 (Merck 230-400 mesh) eluting with EtOAc-n-Hexane (1:3) then (1:1), to afford (RS)-1-(6-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol as a white solid (972 mg, 2.56 mmol, 67.3%), Mp. 91-94° C., MS m/e=380.3 (M+H+).

Workup

  1. customevaporation of the solvent the crude material
  2. extractionthe aqueous phase was extracted with CH2Cl2 (2×100 ml)
  3. washwashed with satd
  4. dry with materialNaCl solution (50 ml), dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. washeluting with EtOAc-n-Hexane (1:3)

Sources & evidence

ORD record
ord-2c27c0093caa4b1ba4895e4b77033973
Source dataset
uspto-grants-2002_03
Patent number
US06359138B1

Reaction notes

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