Hydrochloric Acid → 4-Piperidinemethanol, 1-(7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo(2,3-d)pyrimidin-4-yl)-

HRID 1253832Notes

Reaction equation

HRID 1253832 reaction equation
[BH4-].[Li+].C([O:5][C:6]([CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15]3[CH:23]([CH3:24])[C:22](=O)[N:21]([C:26]4[C:31]([CH3:32])=[CH:30][C:29]([Br:33])=[CH:28][C:27]=4[CH3:34])[C:16]=3[N:17]=[C:18]([CH3:20])[N:19]=2)[CH2:10][CH2:9]1)=O)C.Cl.[OH-].[Na+]>O1CCCC1.CO>[Br:33][C:29]1[CH:30]=[C:31]([CH3:32])[C:26]([N:21]2[C:16]3[N:17]=[C:18]([CH3:20])[N:19]=[C:14]([N:11]4[CH2:12][CH2:13][CH:8]([CH2:6][OH:5])[CH2:9][CH2:10]4)[C:15]=3[C:23]([CH3:24])=[CH:22]2)=[C:27]([CH3:34])[CH:28]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 4148881Lithium borohydrideHCID 59845595HCID 59845595, compound

Product 1

HCID 104785674-Piperidinemethanol, 1-(7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo(2,3-d)pyrimidin-4-yl)-Yield 86.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of lithium borohydride (2.61 g) in tetrahydrofuran (60 mL) was added a solution of 1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-6-oxo-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidine-4-carboxylic acid ethyl ester (6.0 g) in a mixture of tetrahydrofuran (60 mL) and methanol (3 mL) dropwise over 10 minutes under ice-cooling. The reaction mixture was warmed up to room temperature and stirred for 3 hours. After cooling with an ice-bath, 6 M HCl aqueous solution (30 mL) was added and stirred at room temperature for 1 hour. The solution was made to alkaline (pH=9) with 6 M NaOH aqueous solution, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by a silica gel column chromatography (silica gel: Wako Gel (C200), eluent: hexane/ethyl acetate=1:1) to give {1-[7-(4-bromo-2,6-dimethylphenyl)-2,5-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl}methanol (4.6 g).

Workup

  1. temperaturecooling
  2. temperatureAfter cooling with an ice-bath
  3. stirringstirred at room temperature for 1 hour
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by a silica gel column chromatography (silica gel: Wako Gel (C200), eluent: hexane/ethyl acetate=1:1)

Sources & evidence

ORD record
ord-d1dec7b41ef346e9a6798f4ddf9e3781
Source dataset
uspto-grants-2013_06
Patent number
US08455511B2

Reaction notes

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