Triphenylphosphine → 2,2,2-Trichloroethyl 2-[2-(aminomethyl)-4-chlorophenyl]azetidine-1-carboxylate

HRID 1058261Notes

Reaction equation

HRID 1058261 reaction equation
C1CCN2C(=[N:5]CCC2)CC1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:22][CH2:21][N:20]2[C:23]([O:25][CH2:26][C:27]([Cl:30])([Cl:29])[Cl:28])=[O:24])=[C:15]([CH2:31]O)[CH:14]=1.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[Na+]>C1COCC1.O.CO>[NH2:5][CH2:31][C:15]1[CH:14]=[C:13]([Cl:12])[CH:18]=[CH:17][C:16]=1[CH:19]1[CH2:22][CH2:21][N:20]1[C:23]([O:25][CH2:26][C:27]([Cl:30])([Cl:29])[Cl:28])=[O:24]

Participants

10

Reactant 5

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 186724042,2,2-Trichloroethyl 2-[4-chloro-2-(hydroxymethyl)phenyl]azetidine-1-carboxylate

Product 1

HCID 186723262,2,2-Trichloroethyl 2-[2-(aminomethyl)-4-chlorophenyl]azetidine-1-carboxylateYield 79.7%

Reagents, catalysts & solvents 4

HCID 962WaterCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

DBU (0.209 mL, 1.40 mmol) was added to a stirred solution of 2,2,2-trichloroethyl 2-[4-chloro-2-(hydroxymethyl)phenyl]azetidine-1-carboxylate (0.346 g, 0.927 mmol) and DPPA (0.302 mL, 1.40 mmol) in THF (2 mL) at 0° C. After 2 h the reaction was partitioned between ether and water and the organic layer was washed with 1 M sodium hydroxide solution (2 times) and 1 M HCl solution, dried (Na2SO4) and evaporated in vacuo to an oil. Triphenylphosphine (0.262 g, 1.00 mmol) was added to a stirred solution of this oil in THF (2 mL) and water (4 drops). After 16 h methanol (2 mL), water (1 mL) and sodium hydroxide (1 pellet) were added, the mixture was stirred for a further 15 min and then was partitioned between ether and water. The organic layer was extracted into dilute aqueous acetic acid which was basicified with sodium hydroxide and extracted with ether. This organic layer was dried (Na2SO4) and evaporated in vacuo to an oil which was purified by flash column chromatography on silica (eluting with a chloroform/10% ammonium hydroxide in methanol gradient, 1-4% ammonium hydroxide/methanol) to give 2,2,2-trichloroethyl 2-[2-(aminomethyl)-4-chlorophenyl]azetidine-1-carboxylate (275 mg) as an oil: 1H NMR (CDCl3, 400 MHz) δ 2.11 (m, 1H), 2.78 (m, 1H), 3.77 (br d, J=14.4 Hz, 1H), 3.87 (br d, J=14.4 Hz, 1H), 4.16 (br m, 2H), 4.64 (br m, 2H), 5.63 (br s, 1H), 7.27 (obscured m, 1H), 7.35 (s, 1H), 7.50 (br s, 1H).

Workup

  1. customAfter 2 h the reaction was partitioned between ether and water
  2. washthe organic layer was washed with 1 M sodium hydroxide solution (2 times) and 1 M HCl solution
  3. dry with materialdried (Na2SO4)
  4. customevaporated in vacuo to an oil
  5. customwas partitioned between ether and water
  6. extractionThe organic layer was extracted into dilute aqueous acetic acid which
  7. extractionextracted with ether
  8. dry with materialThis organic layer was dried (Na2SO4)
  9. customevaporated in vacuo to an oil which
  10. customwas purified by flash column chromatography on silica (
  11. washeluting with a chloroform/10% ammonium hydroxide in methanol gradient, 1-4% ammonium hydroxide/methanol)

Sources & evidence

ORD record
ord-f12da4da33ea485993468b3b30686b55
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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