Formaldehyde → (R)-t-butyl 2-[3-(1-pyrrolidinyl)-1-propynyl]-1-pyrrolidinecarboxylate

HRID 653842Notes

Reaction equation

HRID 653842 reaction equation
[C:1]([C@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])#[CH:2].O1[CH2:20][CH2:19]OCC1.[NH:21]1[CH2:25]C[CH2:23][CH2:22]1.C=O>C(O)(=O)C>[N:21]1([CH2:25][C:2]#[C:1][C@H:3]2[CH2:7][CH2:6][CH2:5][N:4]2[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:20][CH2:19][CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 31268PyrrolidineHCID 312751,4-DioxaneHCID 10262067tert-butyl (2R)-2-ethynylpyrrolidine-1-carboxylate

Product 1

HCID 9860463(R)-t-butyl 2-[3-(1-pyrrolidinyl)-1-propynyl]-1-pyrrolidinecarboxylate

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 3.5 g of (R)-2-ethynyl-1-pyrrolidinecarboxylic acid, 1,1-dimethylethyl ester, 75 ml dry dioxane, 3.0 ml pyrrolidine, 1.43 g of paraformaldehyde, 7.0 ml of glacial acetic acid and 50 mg of cuprous chloride is stirred at room temperature for 15 minutes then refluxed for 2 hours. The reaction is cooled and concentrated in vacuo. The residue is partitioned between water and methylene chloride and the pH of the mixture is adjusted to pH 11 with ammonium hydroxide. The basified reaction is extracted with methylene chloride and dried over sodium sulfate. The methylene chloride solution is passed over hydrous magnesium silicate and concentrated in vacuo to give 5.65 g of a dark yellow oil. The product is purified by chromatography using deactivated alumina as the absorbant, to give 0.55 g of the product as a pale yellow oil, [α]D26° =+100.6°±0.8 (C=1.22%, methylene chloride).

Workup

  1. temperaturethen refluxed for 2 hours
  2. temperatureThe reaction is cooled
  3. concentrationconcentrated in vacuo
  4. customThe residue is partitioned between water and methylene chloride
  5. customThe basified reaction
  6. extractionis extracted with methylene chloride
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3466e77e8a194d3b91d90e6a4c60987b
Source dataset
uspto-grants-1992_07
Patent number
US05128483

Reaction notes

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