Hydrochloric Acid → HCID 69138262, compound

HRID 1062712Notes

Reaction equation

HRID 1062712 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].[CH3:6][C:7]1([CH3:22])[C:11](=[O:12])[N:10]([C@@H:13]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:14]([OH:16])=[O:15])[C:9](=[O:21])[NH:8]1.[CH3:23][C:24]1(C)[C:28](=O)[N:27]([C@@H](CC2CC2)C(O)=O)[C:26](=[O:38])[NH:25]1.N[C@H:41]([C:46](O)=O)[CH2:42][CH:43]([CH3:45])[CH3:44].CN1CCN(C)[C:51]1=[O:56].Cl.[CH2:58]1COCC1>CN1CCCC1=O>[CH3:22][C:7]1([CH3:6])[C:11](=[O:12])[N:10]([C@@H:13]([CH2:17][CH:18]([CH3:19])[CH3:20])[C:14]([OH:16])=[O:15])[C:9](=[O:21])[N:8]1[CH2:4][C:3]1[CH:23]=[CH:24][C:28]([NH:27][C:26]([NH:25][C:42]2[CH:41]=[CH:46][CH:58]=[CH:45][C:43]=2[CH3:44])=[O:38])=[C:1]([O:56][CH3:51])[CH:2]=1

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 6106L-LeucineHCID 66611,3-Dimethyl-2-imidazolidinoneHCID 8028TetrahydrofuranHCID 11402201HCID 11402201, compoundHCID 69108488HCID 69108488, compoundHCID 178418339Butyllithium

Product 1

HCID 69138262HCID 69138262, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
0 °C

Procedure

16.5 mL of an n-butyllithium solution (2.5M in hexane) were added, under argon and at −40° C., to a solution of 5 g (20.66 mmol) of (S)-2-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-4-methylpentanoic acid (prepared in analogy with examples 1c) and 1d) using L-leucine in place of (S)-2-amino-3-cyclopropylpropionic acid) in 125 mL of absolute THF. The reaction mixture was allowed to warm to 0° C. and a solution of 6.28 g (20.66 mmol) of the compound of example 1b) in 40 mL of N-methyl-2-pyrrolidone and 20 mL of 1,3-dimethyl-2-imidazolidone was added. The reaction mixture was stirred at 0° C. for 1 h. 30 mL of 1N hydrochloric acid were then added and the THF was removed in vacuo. The residue was poured onto 300 mL of water. The precipitate was filtered off with suction, washed with water and taken up in dichloromethane. The solution was then added dropwise to 600 mL of methyl tert-butyl ether. The precipitate was filtered off and the organic phase was dried over magnesium sulfate. The desiccant was filtered off and the solvent was removed in vacuo. The residue was purified by means of preparative HPLC. 2.84 g (27%) of the title compound were obtained after concentrating the product fractions and subsequent freeze-drying.

Workup

  1. customthe THF was removed in vacuo
  2. additionThe residue was poured onto 300 mL of water
  3. filtrationThe precipitate was filtered off with suction
  4. washwashed with water
  5. additionThe solution was then added dropwise to 600 mL of methyl tert-butyl ether
  6. filtrationThe precipitate was filtered off
  7. dry with materialthe organic phase was dried over magnesium sulfate
  8. filtrationThe desiccant was filtered off
  9. customthe solvent was removed in vacuo
  10. customThe residue was purified by means of preparative HPLC

Sources & evidence

ORD record
ord-2f857273e770430d9b6f5ea8afba0bf7
Source dataset
uspto-grants-2005_11
Patent number
US06962937B2

Reaction notes

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