4-Methylmorpholine → Boc-3-cyano-(L)-phenylalanine-4-methylsulfonylpiperazide

HRID 974948Notes

Reaction equation

HRID 974948 reaction equation
Cl.[CH3:2][S:3]([N:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)(=[O:5])=[O:4].CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.[C:29]([NH:36][C@H:37]([C:47](O)=[O:48])[CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([C:45]#[N:46])[CH:40]=1)([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30].C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.C1COCC1>[CH3:2][S:3]([N:6]1[CH2:11][CH2:10][N:9]([C:47](=[O:48])[C@H:37]([CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([C:45]#[N:46])[CH:40]=2)[NH:36][C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[CH2:8][CH2:7]1)(=[O:5])=[O:4]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 2734498(2S)-2-{[(tert-butoxy)carbonyl]amino}-3-(3-cyanophenyl)propanoic acidHCID 162656121-Methanesulfonylpiperazine hydrochloride

Product 1

HCID 131719883Boc-3-cyano-(L)-phenylalanine-4-methylsulfonylpiperazide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

4.92 g (24.5 mmol) of 1-methylsulfonylpiperazine hydrochloride and 2.7 ml (24.5 mmol) of NMM was dissolved in 50 ml of DMF. After addition of 4 g (29.6 mmol) of HOBt and a solution of 5.93 g (20.4 mmol) of Boc-3-cyano-(L)-phenylalanine in 200 ml of THF, the mixture was cooled to O° C. 5.1 g (24.7 mmol) of DCC were added and the mixture was stirred for 48 hours at room temperature. Afterwards, the precipitated dicyclohexyl urea was filtered off, the THF moiety of the solution evaporated under reduced pressure, filtered and the filtrate poured into a mixture of 100 ml of 5% sodium bicarbonate solution and 200 ml of ice water. The formed precipitate was filtered off, washed with water, dissolved in methanol and the solvent was evaporated under reduced pressure. To remove the still present water, a co-distillation with toluene/isopropanol was performed several times. The only slightly impure product was processed in this form. Yield: 7.9 g (89%)

Workup

  1. filtrationAfterwards, the precipitated dicyclohexyl urea was filtered off
  2. customthe THF moiety of the solution evaporated under reduced pressure
  3. filtrationfiltered
  4. additionthe filtrate poured into a mixture of 100 ml of 5% sodium bicarbonate solution and 200 ml of ice water
  5. filtrationThe formed precipitate was filtered off
  6. washwashed with water
  7. dissolutiondissolved in methanol
  8. customthe solvent was evaporated under reduced pressure
  9. customTo remove the still present water

Sources & evidence

ORD record
ord-4bd99622e3064d3ea1dfc1bbd73f19fe
Source dataset
uspto-grants-1997_03
Patent number
US05607937

Reaction notes

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