Triphenyl Phosphate → (3S, 5R)-1-(2,4-dimethoxy-benzyl)-3,5-dimethyl-4-trifluoroacetyl-piperazin-2-one

HRID 1432905Notes

Reaction equation

HRID 1432905 reaction equation
[CH3:1][O:2][C:3]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:4]=1[CH2:5][N:6]([CH2:18][C@@H:19](O)[CH3:20])[C:7](=[O:17])[C@@H:8]([NH:10][C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH3:9].C1(OP(OC2C=CC=CC=2)(OC2C=CC=CC=2)=O)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:4]=1[CH2:5][N:6]1[CH2:18][C@@H:19]([CH3:20])[N:10]([C:11](=[O:16])[C:12]([F:14])([F:13])[F:15])[C@@H:8]([CH3:9])[C:7]1=[O:17]

Participants

5

Reactant 3

HCID 8289Triphenyl PhosphateHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 86592544(2S, 2S)-N-(2,4-Dimethoxy-benzyl)-N-(2-hydroxypropyl)-2-(2,2,2-trifluoroacetylamino)-propionamide

Product 1

HCID 57171471(3S, 5R)-1-(2,4-dimethoxy-benzyl)-3,5-dimethyl-4-trifluoroacetyl-piperazin-2-oneYield 43.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2S, 2S)-N-(2,4-Dimethoxy-benzyl)-N-(2-hydroxypropyl)-2-(2,2,2-trifluoroacetylamino)-propionamide (3.64 g, 9.29 mmol) is dissolved in 25 mL of tetrahydrofuran. Triphenylphosphate (3.65 g, 14.0 mmol) is added, and the resulting mixture is cooled to 0° C. before diethyl azodicarboxylate (2.2 mL, 14 mmol) is added slowly. The resulting mixture is left to stir overnight. The reaction mixture is condensed, and the residue is purified by column chromatography (SiO2, 25% ethyl acetate/hexane). The desired product, (3S, 5R)-1-(2,4-dimethoxy-benzyl)-3,5-dimethyl-4-trifluoroacetyl-piperazin-2-one (1.5 g, 43% yield), is isolated as a clear oil.

Workup

  1. additionis added slowly
  2. waitThe resulting mixture is left
  3. customcondensed
  4. customthe residue is purified by column chromatography (SiO2, 25% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d0c248c53bfe4d62a63af17d0d0d2e4c
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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