Chloroiodomethane → chloromethyl 5-(N-CBz-L-valyloxy)-2,2-dimethylvalerate

HRID 989948Notes

Reaction equation

HRID 989948 reaction equation
[C:1]([NH:11][C@H:12]([C:16]([O:18][CH2:19][CH2:20][CH2:21][C:22]([CH3:27])([CH3:26])[C:23]([OH:25])=[O:24])=[O:17])[CH:13]([CH3:15])[CH3:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl:46][CH2:47]I>O1CCOCC1>[C:1]([NH:11][C@H:12]([C:16]([O:18][CH2:19][CH2:20][CH2:21][C:22]([CH3:27])([CH3:26])[C:23]([O:25][CH2:47][Cl:46])=[O:24])=[O:17])[CH:13]([CH3:14])[CH3:15])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]

Participants

5

Reactant 3

HCID 11644ChloroiodomethaneHCID 2723671Tetrabutylammonium HydroxideHCID 233875555-(N-CBz-L-valyloxy)-2,2-dimethylvaleric acid

Product 1

HCID 23387570chloromethyl 5-(N-CBz-L-valyloxy)-2,2-dimethylvalerateYield 59.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 5-(N-CBz-L-valyloxy)-2,2-dimethylvaleric acid (5.88 g, 15.5 mmol) in dioxane (100 mL), was added dropwise a 40% aqueous solution of tetrabutylammonium hydroxide (10.1 g). After stirring for 5 min, the solution was evaporated to dryness through co-evaporation with dioxane and toluene. The residue was dissolved in dichloromethane (100 mL) and then chloroiodomethane (1.3 mL, 155 mmol) was added and the solution was stirred for 6 h at room temperature. The solution was concentrated under reduced pressure and the residue was shaken with hexane/ethyl acetate (1:1 v/v, 200 mL). The yellow crystalline solid was filtered off and the filtrate was washed with aqueous solution of sodium thiosulfate (0.1 M) and the filtered through anhydrous sodium sulfate and evaporated to dryness. The residue was column chromatographed (silica gel, 1-4% MeOH in CH2C2), to give 3.95 g of chloromethyl 5-(N-CBz-L-valyloxy)-2,2-dimethylvalerate.

Workup

  1. customthe solution was evaporated to dryness through co-evaporation with dioxane and toluene
  2. dissolutionThe residue was dissolved in dichloromethane (100 mL)
  3. stirringthe solution was stirred for 6 h at room temperature
  4. concentrationThe solution was concentrated under reduced pressure
  5. stirringthe residue was shaken with hexane/ethyl acetate (1:1 v/v, 200 mL)
  6. filtrationThe yellow crystalline solid was filtered off
  7. washthe filtrate was washed with aqueous solution of sodium thiosulfate (0.1 M)
  8. filtrationthe filtered through anhydrous sodium sulfate
  9. customevaporated to dryness
  10. customchromatographed (silica gel, 1-4% MeOH in CH2C2)

Sources & evidence

ORD record
ord-3ad558542bd141dfa9e51b925849f857
Source dataset
uspto-grants-2002_10
Patent number
US06458772B1

Reaction notes

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