Trifluoroacetic acid → (2R,5S)-1-(4-fluorobenzyl)-2-(benzyloxy)methyl-5-methylpiperazine-3,6-dione

HRID 489196Notes

Reaction equation

HRID 489196 reaction equation
C[O:2][C:3](=O)[C@H:4]([N:14]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=1)[C:15]([C@@H:17]([NH:19]C(OC(C)(C)C)=O)[CH3:18])=[O:16])[CH2:5][O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[F:34][C:31]1[CH:32]=[CH:33][C:28]([CH2:27][N:14]2[C:15](=[O:16])[C@H:17]([CH3:18])[NH:19][C:3](=[O:2])[C@H:4]2[CH2:5][O:6][CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:29][CH:30]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 54252812(2R)-3-benzyloxy-2-(N-(4-fluorobenzyl)-N-(((1S)-1-(t-butoxycarbonylamino)ethyl)carbonyl)amino)propanoic acid methyl ester

Product 1

HCID 57194490(2R,5S)-1-(4-fluorobenzyl)-2-(benzyloxy)methyl-5-methylpiperazine-3,6-dioneYield 84.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2R)-3-benzyloxy-2-(N-(4-fluorobenzyl)-N-(((1S)-1-(t-butoxy-carbonylamino)ethyl)carbonyl)amino)propanoic acid methyl ester (2.0 g, 4 mmol) in CH2Cl2 (25 mL) was cooled to 0° C. and trifluoroacetic acid (25 mL) was added dropwise over 2 hours. At the end of the addition, the ice bath was removed and the mixture was stirred at ambient temperature. After 2 hours, the mixture was concentrated in vacuo. The residual yellow oil was taken up in ethyl acetate and washed with 1 N aqueous NaHCO3 solution. The organic layer was separated then dried over MgSO4, filtered, and concentrated in vacuo to afford 1.2 g (83% yield) of (2R,5S)-1-(4-fluorobenzyl)-2-(benzyloxy)methyl-5-methylpiperazine-3,6-dione, a compound of formula (R), as a clear oil; NMR (CDCl3) 7.4-7.2 (m, 7), 7.0 (dd, 2), 5.0 (1), 4.5-4.0 (m, 4), 3.9-3.5 (m, 4), 1.5 (d, 3) ppm, MS (LSIMS) 356.

Workup

  1. additionAt the end of the addition
  2. customthe ice bath was removed
  3. concentrationthe mixture was concentrated in vacuo
  4. washwashed with 1 N aqueous NaHCO3 solution
  5. customThe organic layer was separated
  6. dry with materialthen dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3a64943e86e0400e8b92b5a1588462d4
Source dataset
uspto-grants-2005_12
Patent number
US06977258B2

Reaction notes

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