Imidazole → tert-Butyl 3-(2-iodoethyl)azetidine-1-carboxylate

HRID 246433Notes

Reaction equation

HRID 246433 reaction equation
O[CH2:2][CH2:3][CH:4]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N1C=CN=C1.[I:39]I>O.C(#N)C>[I:39][CH2:2][CH2:3][CH:4]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5]1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 22594530tert-Butyl 3-(2-hydroxyethyl)azetidine-1-carboxylate

Product 1

HCID 19034125tert-Butyl 3-(2-iodoethyl)azetidine-1-carboxylateYield 69.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A stirred solution of tert-butyl 3-(2-hydroxyethyl)azetidine-1-carboxylate (254 mg, 1.26 mmol), Ph3P (381 mg, 1.45 mmol.15), imidazole (129 mg, 1.89 mmol0) and acetonitrile (6.5 mL) at 0° C.; was treated with iodine (368 mg, 1.45 mmol.15). Mixture was allowed to reach 25° C. and stirring continued for 18 h. The reaction mixture was then diluted with water and extracted with hexanes (6×25 mL). The combined organics were dried (MgSO4) and concentrated, then purified by chromatography (40 g column, 50 μm from Analogix, 0-30% EtOAc in hexanes over 15 min to give tert-butyl 3-(2-iodoethyl)azetidine-1-carboxylate (271 mg, 871 μmol, 69.0%) as a colorless oil. 1H NMR (CDCl3) δ: 4.03 (t, J=8.3 Hz, 2H), 3.56 (dd, J=8.7, 5.7 Hz, 2H), 3.10 (t, J=7.0 Hz, 2H), 2.63 (quint, J=7.8, 5.4 Hz, 1H), 2.13 (q, J=7.1 Hz, 2H), 1.42 (s, 9H).

Workup

  1. customat 0° C.
  2. customto reach 25° C.
  3. extractionextracted with hexanes (6×25 mL)
  4. dry with materialThe combined organics were dried (MgSO4)
  5. concentrationconcentrated
  6. custompurified by chromatography (40 g column, 50 μm from Analogix, 0-30% EtOAc in hexanes over 15 min

Sources & evidence

ORD record
ord-667fd235df814df39b31b1afd1a5d265
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…