Iodine → 1-(t-butoxycarbonyl)-4(N-acetyl-L-methionyl)piperazine

HRID 863657

Reaction equation

HRID 863657 reaction equation
[C:1]([NH:4][C@H:5]([C:10]([OH:12])=O)[CH2:6][CH2:7][S:8][CH3:9])(=[O:3])[CH3:2].C1(N=C=NC2CCCCC2)CCCCC1.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29].II.C1C=C2C(C(O)(O)C(=O)C2=CC=1)=O>ClCl.ClCCl.C(O)(=O)C.O1CCCC1.C(#N)C>[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][N:38]([C:10](=[O:12])[C@H:5]([CH2:6][CH2:7][S:8][CH3:9])[NH:4][C:1](=[O:3])[CH3:2])[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

11

Reactant 5

HCID 807IodineHCID 10236NinhydrinHCID 10868DicyclohexylcarbodiimideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 448580N-acetyl-L-methionine

Product 1

HCID 544692851-(t-butoxycarbonyl)-4(N-acetyl-L-methionyl)piperazineYield 108.6%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidCatalystHCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 24526ChlorineSolvent

Procedure

A solution of 4.78 g (0.025 mol) of N-acetyl-L-methionine in CH2 Cl2 : acetonitrile (120 ml) was cooled to 0° C. To this solution was added 5.36 g (0.025 mol) of dicyclohexylcarbodiimide (DCC) followed by the rapid addition of 3.90 g (0.021 mol) of N-t-butoxycarbonylpiperazine in 6 ml of dichloromethane. The progress of the reaction was followed on silica gel TLC plates developed with 4:1 acetonitrile: tetrahydrofuran and visualized with either iodine or ninhydrin spray. The reaction was complete within 2 h. A few drops of glacial acetic acid were added to the reaction mixture and the solvent was removed on a rotary evaporator. The residue was taken up in ether and filtered. The clear filtrate was washed with dilute acid followed by dilute base. The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and evaporated to give 8.2 g of 1-(t-butoxycarbonyl)-4-(N-acetyl-L-methionyl)piperazine, a colorless oil which required no further purification: IR (film) 3304, 3058, 2973, 2931, 2868, 1701, 1645, 1539, 1420, 1237, 1173 cm-1 ; NMR (CDCl3) δ 1.47 (s, 9 H), 1.80 (m, 2 H), 2.02 (s, 3 H), 2.10 (s, 3 H), 2.46 (m, 2 H), 3.53 (m, 8 H), 5.10 (M, 1 H), 6.35 (b, 0.5 H), 6.43 (b, 0.5 H).

Workup

  1. customthe solvent was removed on a rotary evaporator
  2. filtrationfiltered
  3. washThe clear filtrate was washed
  4. additionwith dilute acid
  5. additionby dilute base
  6. customThe organic layer was separated
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-328ba9ba46df41aebcb1abc9208b3ee4
Source dataset
uspto-grants-1998_02
Patent number
US05721365

Linked notes

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