Dimethylamine, hydrochloride → (2S,4R)-tert-butyl 2-(dimethylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

HRID 1948921Notes

Reaction equation

HRID 1948921 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:16][C@H:14]([OH:15])[CH2:13][C@H:9]1[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:18][NH:19][CH3:20]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:16][C@H:14]([OH:15])[CH2:13][C@H:9]1[C:10](=[O:11])[N:19]([CH3:20])[CH3:18])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 10473Dimethylamine, hydrochlorideHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 25180889(2S,4R)-tert-butyl 2-(dimethylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylateYield 45.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

1-[3-(Dimethylamino)propyl]-3-ethylearbodiimide hydrochloride (2.48 g) was added to a stirred suspension of N-tert-butoxycarbonyl-L-hydroxyproline (2.0 g), 4-(dimethylamino)pyridine (5.28 g) and dimethylamine hydrochloride (1.4 g) in methylene chloride (100 ml) and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with citric acid (1.0 M), saturated sodium bicarbonate and saturated brine before drying over magnesium sulfate. The product was then purified by column chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10). The fractions containing the expected product were combined and evaporated under vacuum to give (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2-(N,N-dimethylcarbamoyl)pyrrolidine as a colourless gum (1.01 g); 1H NMR Spectrum: (DMSO d6) 1.29-1.40 (m, 9H), 1.74-1.83 (m, 1H), 2.04-2.15 (m, 1H), 2.80-2.87 (m, 3H), 3.03 (s, 3H), 3.26 (m, 1H), 3.40 (m, 1H), 4.28 (m, 1H), 4.64 (m, 1H), 4.95 (d, 1H).

Workup

  1. washThe reaction mixture was washed with citric acid (1.0 M), saturated sodium bicarbonate and saturated brine
  2. dry with materialbefore drying over magnesium sulfate
  3. customThe product was then purified by column chromatography on silica eluting
  4. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10)
  5. additionThe fractions containing the expected product
  6. customevaporated under vacuum

Sources & evidence

ORD record
ord-aa3e772901f24a89bf61ae9554e8ab5a
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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