Sodium Hydroxide → HCID 12042612, compound

HRID 2230205Notes

Reaction equation

HRID 2230205 reaction equation
C[O:2][C:3](=[O:39])[C@H:4]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([NH:28][C:29]([C:31]2[C:36]([Cl:37])=[CH:35][CH:34]=[CH:33][C:32]=2[Cl:38])=[O:30])=[CH:24][CH:23]=1)[NH:5][C:6]([C:8]1([CH2:13][CH2:14][CH2:15][CH2:16][S:17]([CH3:20])(=[O:19])=[O:18])[CH2:12][CH2:11][CH2:10][CH2:9]1)=[S:7].[OH-].[Na+]>C(O)C.O.C(OCC)C>[Cl:38][C:32]1[CH:33]=[CH:34][CH:35]=[C:36]([Cl:37])[C:31]=1[C:29]([NH:28][C:25]1[CH:26]=[CH:27][C:22]([CH2:21][C@@H:4]([C:3]([OH:39])=[O:2])[NH:5][C:6]([C:8]2([CH2:13][CH2:14][CH2:15][CH2:16][S:17]([CH3:20])(=[O:19])=[O:18])[CH2:9][CH2:10][CH2:11][CH2:12]2)=[S:7])=[CH:23][CH:24]=1)=[O:30]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 12042611HCID 12042611, compound

Product 1

HCID 12042612HCID 12042612, compoundYield 70.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
52.5 °C

Procedure

To a solution of 4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[1-[4-(methylsulfonyl)butyl]cyclopentyl]thioxomethyl]-L-phenylalanine methyl ester (25.86 mmol, 15.87 g) in ethanol (75 mL) was added aqueous 1.0N sodium hydroxide (60 mL) at 50° C. The mixture was heated to 50-55° C. and the resulting clear light brown solution was stirred for 22 h at which time TLC analysis of the mixture indicated the absence of starting material. The mixture was diluted with water and allowed to cool to room temperature and was filtered to remove a small amount of solids. The filtrate was concentrated and the residual aqueous solution was washed with diethyl ether (2×75 mL). The basic aqueous layer was acidified with 3.0N HCl to form a cloudy suspension and was extracted with ethyl acetate (3×100 mL). The combined ethyl acetate extracts were washed with brine (200 mL) then the dried (MgSO4) solution was filtered and evaporated to dryness. The residue was taken up in dichloromethane and diluted with diethyl ether:hexane (1:1) to obtain a solid which was collected by filtration. Trituration of the solid with hot ethyl acetate (˜100 mL) resulted in a suspension that was then diluted with diethyl ether (˜50 mL) and the solid was collected by filtration. The above Trituration was repeated to afford 10.89 g (70%) of 4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[1-[4-(methylsulfonyl)butyl]cyclopentyl]thioxomethyl]-L-phenylalanine as a colorless solid. HR MS: Obs. mass, 599.1193. Calcd. mass, 599.1208 (M+H).

Workup

  1. temperatureto cool to room temperature
  2. filtrationwas filtered
  3. customto remove a small amount of solids
  4. concentrationThe filtrate was concentrated
  5. washthe residual aqueous solution was washed with diethyl ether (2×75 mL)
  6. customto form a cloudy suspension
  7. extractionwas extracted with ethyl acetate (3×100 mL)
  8. washThe combined ethyl acetate extracts were washed with brine (200 mL)
  9. dry with materialthe dried (MgSO4) solution
  10. filtrationwas filtered
  11. customevaporated to dryness
  12. additiondiluted with diethyl ether:hexane (1:1)
  13. customto obtain a solid which
  14. filtrationwas collected by filtration
  15. customTrituration of the solid with hot ethyl acetate (˜100 mL) resulted in a suspension that
  16. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-a2b0741d06c042cdab6efa48a9ae961c
Source dataset
uspto-grants-2002_07
Patent number
US06423728B1

Reaction notes

Loading…