3-Chlorobenzyl alcohol → N-{1-[2-(azidomethyl)-4-chlorophenyl]-2,2,2-trifluoroethyl}-N-(4-methoxyphenyl)amine

HRID 1058229Notes

Reaction equation

HRID 1058229 reaction equation
C1CCN2C(=NCCC2)CC1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[C:20]([F:23])([F:22])[F:21])=[C:15]([CH2:33]O)[CH:14]=1.ClC1C=C(C=CC=1)CO.C1C=CC(P([N:58]=[N+:59]=[N-:60])(C2C=CC=CC=2)=O)=CC=1>C1COCC1>[N:58]([CH2:33][C:15]1[CH:14]=[C:13]([Cl:12])[CH:18]=[CH:17][C:16]=1[CH:19]([NH:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1)[C:20]([F:23])([F:22])[F:21])=[N+:59]=[N-:60]

Participants

6

Reactant 4

HCID 701173-Chlorobenzyl alcoholHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 18672368N-{1-[4-chloro-2-(hydroxymethyl)phenyl]-2,2,2-trifluoroethyl}-N-(4-methoxyphenyl)amine

Product 1

HCID 18672426N-{1-[2-(azidomethyl)-4-chlorophenyl]-2,2,2-trifluoroethyl}-N-(4-methoxyphenyl)amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DBU (0.483 mL, 3.23 mmol) was added to a stirred solution of N-{1-[4-chloro-2-(hydroxymethyl)phenyl]-2,2,2-trifluoroethyl}-N-(4-methoxyphenyl)amine (0.46 g of a 1:1.7 mixture with 3-chlorobenzyl alcohol) and DPPA (0.696 mL, 3.23 mmol) in THF (4 mL) at 0° C. The mixture was warmed to ambient temperature and after 3 h was partitioned between ether and water. The organic layer was washed with 1 M sodium hydroxide solution and brine, dried (Na2SO4) and evaporated to an oil which was purified by flash column chromatography on silica (eluting with 5% methylene chloride, 0-15% ethyl acetate/hexanes) to give N-{1-[2-(azidomethyl)-4-chlorophenyl]-2,2,2-trifluoroethyl}-N-(4-methoxyphenyl)amine (0.199 g) as an oil: 1H NMR (CDCl3, 400 MHz) δ 3.72 (s, 3H), 3.97 (d, J=7.3 Hz, 1H), 4.37 (d, J=14.1 Hz, 1H), 4.48 (d, J=14.1 Hz, 1H), 5.20 (pentet, J=7.1 Hz, 1H), 6.63 (d, J=9.0 Hz, 2H), 6.75 (d, J=9.0 Hz, 2H), 7.37 (m, 2H), 7.55 (d, J=8.2 Hz, 1H).

Workup

  1. customwas partitioned between ether and water
  2. washThe organic layer was washed with 1 M sodium hydroxide solution and brine
  3. dry with materialdried (Na2SO4)
  4. customevaporated to an oil which
  5. customwas purified by flash column chromatography on silica (eluting with 5% methylene chloride, 0-15% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7f0993ecb395485582ffa09bda922126
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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