Triphenylphosphine → 3-Amino-1-(diphenylmethyl)azetidine

HRID 2374151Notes

Reaction equation

HRID 2374151 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16](OS(C)(=O)=O)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:23]=[N+]=[N-].[Na+].C([O-])(O)=O.[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH4+].[OH-]>CN(C=O)C.C1COCC1.O>[CH:1]([N:14]1[CH2:17][CH:16]([NH2:23])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 11776TriphenylphosphineHCID 14923Ammonium HydroxideHCID 33557Sodium AzideHCID 516892Sodium BicarbonateHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonate

Product 1

HCID 57445463-Amino-1-(diphenylmethyl)azetidineYield 80.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Methanesulfonic acid 1-benzhydryl-azetidin-3-yl ester (14.8 g, 47 mmol, Oakwood Products) was dissolved in anhydrous DMF (60 mL), and to this solution was added sodium azide (9.0 g, 138 mmol). The mixture was heated (80° C.) for 18 h, cooled to RT, then treated with water (20 mL) and satd. aq. NaHCO3 (20 mL). The resulting mixture was extracted with DCM (4×60 mL) and the organic layer dried over Na2SO4. Solvent removal yielded a crude oil (11 g) that was redissolved in THF (85 mL) and treated with triphenyl phosphine (15 g, 57 mmol). After stirring at RT (30 min; gas evolution and some exotherm noted), the mixture was heated to reflux (6 h), then cooled back down to RT before adding NH4OH (7 mL) and refluxing again (5 h). After cooling to RT, the solvent was removed and the residue treated with 3N HCl (35 mL) giving a pH 1. The resulting acidic solution was extracted with DCM (3×50 mL) and the organic layers were discarded. The aqueous layer was then basified with solid potassium hydroxide to pH 10 and then extracted again with DCM (3×75 mL). The aqueous layer was then satd. with solid sodium chloride and re-extracted with DCM (3×75 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated to yield crude 1-benzhydryl-azetidin-3-ylamine (9.0 g, 37.8 mmol). MS (ESI+) for m/z (M+H)+239.

Workup

  1. temperaturecooled to RT
  2. extractionThe resulting mixture was extracted with DCM (4×60 mL)
  3. dry with materialthe organic layer dried over Na2SO4
  4. customSolvent removal
  5. customyielded a crude oil (11 g) that
  6. temperaturegas evolution and some exotherm noted), the mixture was heated
  7. temperatureto reflux (6 h)
  8. temperaturecooled back down to RT
  9. temperaturerefluxing again (5 h)
  10. temperatureAfter cooling to RT
  11. customthe solvent was removed
  12. additionthe residue treated with 3N HCl (35 mL)
  13. customgiving a pH 1
  14. extractionThe resulting acidic solution was extracted with DCM (3×50 mL)
  15. extractionextracted again with DCM (3×75 mL)
  16. extractionwith solid sodium chloride and re-extracted with DCM (3×75 mL)
  17. dry with materialThe combined organic layers were dried over Na2SO4
  18. filtrationfiltered
  19. concentrationconcentrated

Sources & evidence

ORD record
ord-33e94840a7834d5a924894cac7e2a594
Source dataset
uspto-grants-2008_12
Patent number
US07462600B2

Reaction notes

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