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

HRID 278419Notes

Reaction equation

HRID 278419 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([CH2:13][N:14]1[CH2:19][CH2:18][C:17]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=3)([OH:20])[CH2:16][CH2:15]1)[CH2:7][CH2:6]2.B(Br)(Br)Br.C(Cl)Cl.CO.C([O-])(O)=O.[Na+]>C(Cl)Cl.O>[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([CH2:13][N:14]1[CH2:19][CH2:18][C:17]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=3)([OH:20])[CH2:16][CH2:15]1)[CH2:7][CH2:6]2

Participants

7

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 22277759Boron tribromide dichloromethaneHCID 22628368(RS)-1-(6-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol

Product 1

HCID 9842071(RS)-1-(6-hydroxy-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-olYield 616.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To (RS)-1-(6-methoxy-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol (843 mg, 2.22 mmol) in CH2Cl2 (20 ml) was added 1M BBr3/CH2Cl2 (4.88 ml, 4.88 mmol, 2.2 eq.) over 15 min at −78° C., the mixture was then allowed to warm to RT over 40 min. MeOH (3 ml), H2O (20 ml) and NaHCO3 (20 ml) were added and the mixture extracted with CH2Cl2 (4×50 ml). The extracts were washed with satd. NaCl solution (30 ml), dried (Na2SO4), filtered and evaporated, to afford the crude product as a yellow foam. Chromatography over SiO2 (Merck 230-400 mesh) eluting with CH2Cl2—MeOH (97:3) afforded (RS)-1-(6-hydroxy-1,2,3,4-tetrahydro-naphthalen-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol as a white foam (500 mg, 13.68 mmol, 61%), MS m/e=366.2 (M+H+).

Workup

  1. extractionthe mixture extracted with CH2Cl2 (4×50 ml)
  2. washThe extracts were washed with satd
  3. dry with materialNaCl solution (30 ml), dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto afford the crude product as a yellow foam
  7. washChromatography over SiO2 (Merck 230-400 mesh) eluting with CH2Cl2—MeOH (97:3)

Sources & evidence

ORD record
ord-fc919ed63df14ce78d3b42877bdafac4
Source dataset
uspto-grants-2002_03
Patent number
US06359138B1

Reaction notes

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