Triethylazanium;formate → (S)-3-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 242305Notes

Reaction equation

HRID 242305 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][C:14]2[C:15]3[CH2:23][N:22](CC4C=CC=CC=4)[CH2:21][CH2:20][C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.C([NH+](CC)CC)C>CO.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][C:14]2[C:15]3[CH2:23][NH:22][CH2:21][CH2:20][C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 10219518Triethylazanium;formateHCID 57495302(S)-3-(6-Benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 57495303(S)-3-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 94%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

Pd(OH)2/C (1.54 g, 2.2 mmol) was flushed with nitrogen, (S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (8.5 g, 20.67 mmol) dissolved in methanol (50 mL) was added followed by the addition of triethylammonium formate (7.9 g, 53.7 mmol). The reaction mixture was refluxed for 1 h, cooled down to room temperature, filtered through a celite pad and the filtrate was partitioned between 2-Me-THF (50 mL) and water (20 mL). The upper organic phase was collected and the bottom aqueous phase was re-extracted with 2-Me-THF (10 mL). All the organic layers were combined and concentrated under vacuum to provide (S)-3-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (6.2 g, 94% yield) as a yellow gum.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was refluxed for 1 h
  3. filtrationfiltered through a celite pad
  4. customthe filtrate was partitioned between 2-Me-THF (50 mL) and water (20 mL)
  5. customThe upper organic phase was collected
  6. extractionthe bottom aqueous phase was re-extracted with 2-Me-THF (10 mL)
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-319ca423cf9f4bc593c91933ee7e0ae9
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Reaction notes

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