Phosphorus sulfide (P2S5) → Phenylmethyl (3S)-3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-(methylamino)-4-thioxobutanoate

HRID 1160400Notes

Reaction equation

HRID 1160400 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([C:21](=O)[NH:22][CH3:23])[CH2:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:7])([CH3:4])[CH3:3].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:26].C([O-])(O)=O.[Na+]>C1COCC1>[CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([C:21]([NH:22][CH3:23])=[S:26])[CH2:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:7])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 14817Phosphorus sulfide (P2S5)HCID 516892Sodium BicarbonateHCID 59516205Boc-Asp(OBzl)-NHMe

Product 1

HCID 59516226Phenylmethyl (3S)-3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-(methylamino)-4-thioxobutanoateYield 125%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Phenylmethyl N2-{[(1,1-dimethylethyl)oxy]carbonyl}-N1-methyl-L-α-asparaginate (4.20 g, 12.48 mmol) and phosphorus pentasulfide (3.33 g, 7.49 mmol) were dissolved in THF (105 mL) and the reagents were stirred at room temperature for 4 h. Saturated NaHCO3 was added and the reaction was extracted with EtOAc. The organic layer was concentrated and the residue was dissolved in CH2Cl2:Et2O (1:1) and filtered through a well packed silica gel column to give the titled product (3.3 g, 75%) as a white solid. 1H-NMR (CDCl3) δ: 1.461 (9H, s), 2.960 (1H, m), 3.149 (3H, d, J=5.2 Hz), 3.270 (1H, m), 4.820 (1H, s), 5.137 (2H, m), 5.770 (1H, s), 7.374 (5H, m), 8.380 (1H, s). LC-MS (ES) m/e 353.6 (M+H)+.

Workup

  1. extractionthe reaction was extracted with EtOAc
  2. concentrationThe organic layer was concentrated
  3. dissolutionthe residue was dissolved in CH2Cl2:Et2O (1:1)
  4. filtrationfiltered through a well packed silica gel column

Sources & evidence

ORD record
ord-9c5817f03b4b4705b6826d66a7d28be0
Source dataset
uspto-grants-2010_10
Patent number
US07816395B2

Reaction notes

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