Diisopropylamine → (R)-5-Hydroxymethyltolterodine

HRID 402849Notes

Reaction equation

HRID 402849 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][C@@H:8](O)[CH2:7][C@@H:6]2[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH:20]([NH:23][CH:24]([CH3:26])[CH3:25])([CH3:22])[CH3:21]>[Pd].CO>[OH:1][CH2:2][C:3]1[CH:12]=[CH:11][C:10]([OH:9])=[C:5]([C@@H:6]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:7][CH2:8][N:23]([CH:24]([CH3:26])[CH3:25])[CH:20]([CH3:22])[CH3:21])[CH:4]=1

Participants

5

Reactant 2

HCID 7912DiisopropylamineHCID 67318206HCID 67318206, compound

Product 1

HCID 9819382(R)-5-Hydroxymethyltolterodine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture consisting of methanol, Pd/C catalyst, (R)-6-hydroxymethyl-4-phenylchroman-2-(R)-ol, and an excess of diisopropyl amine will be hydrogenated at ambient temperature at a pressure of 4 bar. After at least 18 hours, the reaction mixture will be filtered and evaporated to dryness. Subsequently, it is treated with 1 molar equivalent of a solution of lithium aluminium hydride in tetrahydrofuran for cleaving any cyclic hemiaminal. The reaction is quenched with water, and the product will be extracted with ethyl acetate. Removal of the solvent and drying in vacuum provides (R)-4-hydroxymethyl-2-(3-diisopropylamino-1-phenylpropyl)-phenol in the form of a colourless oil.

Workup

  1. customwill be hydrogenated at ambient temperature at a pressure of 4 bar
  2. waitAfter at least 18 hours
  3. filtrationthe reaction mixture will be filtered
  4. customevaporated to dryness
  5. additionSubsequently, it is treated with 1 molar equivalent of a solution of lithium aluminium hydride in tetrahydrofuran
  6. customThe reaction is quenched with water
  7. extractionthe product will be extracted with ethyl acetate
  8. customRemoval of the solvent
  9. customdrying in vacuum

Sources & evidence

ORD record
ord-8280aabb9fdc48f8a7ba991ba988b193
Source dataset
uspto-grants-2014_06
Patent number
US08742140B2

Reaction notes

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