Ammonium Chloride → Tert-butyl (3R,4R)-3-azido-4-hydroxypyrrolidine-1-carboxylate

HRID 1952428Notes

Reaction equation

HRID 1952428 reaction equation
[C:1]([N+:8]1([O-])[CH2:12][CH:11]=[CH:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[N-:14]=[N+:15]=[N-:16].[Na+].[NH4+].[Cl-].C[OH:21].O>>[C:1]([N:8]1[CH2:12][C@@H:11]([OH:21])[C@H:10]([N:14]=[N+:15]=[N-:16])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

5

Reactant 4

HCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 22242641Methanol--water (1/1)HCID 86654475N-Boc-3-pyrroline oxide

Product 1

HCID 15855750Tert-butyl (3R,4R)-3-azido-4-hydroxypyrrolidine-1-carboxylate

Conditions

Temperature
65 °C

Procedure

A mixture of N-Boc-3-pyrroline oxide (0.925 g, 5.0 mmol), NaN3 (0.65 g, 10 mmol), and NH4Cl (5.0 mmol) in MeOH—H2O (6:1, 16 mL) was stirred at 65° C. overnight. The reaction mixture was concentrated under reduced pressure and the residue was extracted thoroughly with ethyl acetate. The combined ethyl acetate extract was washed with water and sat. brine, dried over anhydrous Na2SO4, and evaporated. The crude azidoalcohol was purified by recrystallization from ether-hexane: mp 34-36° C.; 1H NMR (300 MHz, CD3OD) δ 4.16 (m, 1H), 3.95 (m, 1H), 3.62 (m, 1H), 3.51 (m, 1H), 3.35 (m, 2H), 1.47 (s, 9H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. extractionthe residue was extracted thoroughly with ethyl acetate
  3. extractionThe combined ethyl acetate extract
  4. washwas washed with water and sat. brine
  5. dry with materialdried over anhydrous Na2SO4
  6. customevaporated
  7. customThe crude azidoalcohol was purified by recrystallization from ether-hexane

Sources & evidence

ORD record
ord-00dc4db20ac4422faa3cc8048d52b095
Source dataset
uspto-grants-2013_03
Patent number
US08404866B2

Reaction notes

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