Sodium Carbonate → trans-Tert-butyl 3-azido-4-fluoropyrrolidine-1-carboxylate

HRID 928191Notes

Reaction equation

HRID 928191 reaction equation
[N:1]([C@H:4]1[C@H:8](O)[CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]1)=[N+:2]=[N-:3].CCN(S(F)(F)[F:23])CC.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[N:1]([C@H:4]1[C@H:8]([F:23])[CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]1)=[N+:2]=[N-:3]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 123472(Diethylamino)sulfur trifluorideHCID 15855750Tert-butyl (3R,4R)-3-azido-4-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 118081950trans-Tert-butyl 3-azido-4-fluoropyrrolidine-1-carboxylateYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To the solution of (trans)-tert-butyl 3-azido-4-hydroxypyrrolidine-1-carboxylate (120 g, 0.44 mol, 5/6 purity, containing DCM) in DCM (1.2 L) at −78° C. was added dropwise DAST (141 g, 0.88 mol) in DCM (200 mL). After addition, the mixture was stirred at −78° C. for 1 hr, then warmed to rt and stirred overnight. The reaction mixture was poured into sat. Na2CO3 (2 L) slowly then the DCM phase was washed with water (1 L), sat. NaCl and dried over Na2SO4. Concentrated and purified via flash chromatography (petroleum ether/EtOAc 20/1˜10/1) to give the title compound (48 g, 48% yield) as light yellow oil.

Workup

  1. additionAfter addition
  2. temperaturewarmed to rt
  3. stirringstirred overnight
  4. washthe DCM phase was washed with water (1 L), sat. NaCl
  5. dry with materialdried over Na2SO4
  6. concentrationConcentrated
  7. custompurified via flash chromatography (petroleum ether/EtOAc 20/1˜10/1)

Sources & evidence

ORD record
ord-a58aeaab04394b098c285873f89745f9
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

Loading…