Diisopropylamine → (R)-5-Hydroxymethyltolterodine

HRID 626094Notes

Reaction equation

HRID 626094 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-e5877e9510714435b8f76d73554c224d
Source dataset
uspto-grants-2016_04
Patent number
US09309215B2

Reaction notes

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