Methanol → (RS)-2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-ylmethyl]-2,3-dihydro-1H-indol-5-ol

HRID 278416Notes

Reaction equation

HRID 278416 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([CH2:12][N:13]1[CH2:18][CH2:17][C:16]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)([OH:19])[CH2:15][CH2:14]1)[CH2:6]2.B(Br)(Br)Br.C(Cl)Cl.CO.C([O-])(O)=O.[Na+]>C(Cl)Cl>[OH:19][C:16]1([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=2)[CH2:15][CH2:14][N:13]([CH2:12][CH:7]2[CH2:6][C:5]3[C:9](=[CH:10][CH:11]=[C:3]([OH:2])[CH:4]=3)[NH:8]2)[CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 22277759Boron tribromide dichloromethaneHCID 22628339(RS)-1-(5-methoxy-2,3-dihydro-1H-indol-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol

Product 1

HCID 22628336(RS)-2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-ylmethyl]-2,3-dihydro-1H-indol-5-olYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (RS)-1-(5-methoxy-2,3-dihydro-1H-indol-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol (131 mg, 0.357 mol) in CH2Cl2 (10 ml) was added 1M BBr3—CH2Cl2 (2.14 ml, 2.74 mmol, 6 eq.) at −78° C. over 5 min. The reaction was stirred at RT for 48 hr., then MeOH (20 ml) was added followed by 10% NaHCO3 (20 ml), and the aqueous phase extracted with CH2Cl2 (2×50 ml) and the combined extracts washed with satd. NaCl solution (50 ml), dried over (Na2SO4) filtered and evaporated. Purification of the crude product over SiO2 (Merck 230-400 mesh) eluting with CH2Cl2-MeOH (9:1) afforded (RS)-2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-ylmethyl]-2,3-dihydro-1H-indol-5-ol as a brown solid (64.6 mg, 0.183 mmol, 51%), Mp. 90-94° C., MS: m/e=353.3 (M+H+).

Workup

  1. extractionthe aqueous phase extracted with CH2Cl2 (2×50 ml)
  2. washthe combined extracts washed with satd
  3. dry with materialNaCl solution (50 ml), dried over (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customPurification of the crude product over SiO2 (Merck 230-400 mesh)
  7. washeluting with CH2Cl2-MeOH (9:1)

Sources & evidence

ORD record
ord-9134ed391a5848f597214bc77a4bbf57
Source dataset
uspto-grants-2002_03
Patent number
US06359138B1

Reaction notes

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