Sodium Azide → (3S,4S)-benzyl 3-azido-4-methylpyrrolidine-1-carboxylate

HRID 877678Notes

Reaction equation

HRID 877678 reaction equation
[CH3:1][C@H:2]1[C@H:6](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:5][N:4]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:3]1.[N-:28]=[N+:29]=[N-:30].[Na+]>CN(C=O)C.CCOC(C)=O.C(=O)(O)[O-].[Na+]>[N:28]([C@H:6]1[C@@H:2]([CH3:1])[CH2:3][N:4]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:5]1)=[N+:29]=[N-:30]

Participants

6

Reactant 2

HCID 33557Sodium AzideHCID 131732605(+/-)-(trans)-Benzyl 3-methyl-4-(tosyloxy)pyrrolidine-1-carboxylate

Product 1

HCID 86707890(3S,4S)-benzyl 3-azido-4-methylpyrrolidine-1-carboxylateYield 60.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

(+/−)-(trans)-benzyl 3-methyl-4-(tosyloxy)pyrrolidine-1-carboxylate (5.00 g, 12.84 mmol) and sodium azide (2.087 g, 32.1 mmol) in DMF (10 mL) was heated under argon at 85° C. for 18 h. The resulting mixture was cooled and diluted with EtOAc and sat. sodium bicarbonate, washed with water, brine, dried over magnesium sulfate, filtered and concentrated to give a tan oil which was purified via preparative chromatography using Hexanes/EtOAc mixtures as the eluant and 40 g silica cartridge. Fractions containing the major product were combined and concentrated to afford the title compound as a near colorless oil (2.01 g, 7.72 mmol, 60%). HPLC (method B) retention time=3.30 min. LCMS (m+Na)=283.2. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.41-7.30 (m, 5H), 5.15 (d, J=6.2 Hz, 2H), 4.00 (t, J=4.3 Hz, 1H), 3.76-3.55 (m, 3H), 3.16-3.02 (m, 1H), 2.47-2.30 (m, 1H), 1.13 (t, J=7.0 Hz, 3H).

Workup

  1. temperatureThe resulting mixture was cooled
  2. washwashed with water, brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a tan oil which
  7. customwas purified via preparative chromatography
  8. additionFractions containing the major product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-e7d1c932aea441558857ced50033856c
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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