Dichloromethane → HCID 12086024, compound

HRID 617637Notes

Reaction equation

HRID 617637 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:17]=[O:18])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:20]([F:27])([F:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22].ClCCl.S([O-])(O)(=O)=O.[K+]>C1COCC1.[Zn]>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C@@H:17]([OH:18])[C:20]([F:27])([F:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 69585Ethyl bromodifluoroacetateHCID 516920Potassium bisulfateHCID 6998013tert-butyl N-[(2S)-1-oxo-3-phenylpropan-2-yl]carbamate

Product 1

HCID 12086024HCID 12086024, compoundYield 27.1%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of the target compound in step (2) (7.16 g, 28.5 mmol) in dichloromethane (85 mL) were added successively triethylamine (15.8 mL, 113.9 mmol) and a solution of sulfur trioxidepyridine complex (18.1 g, 113.9 mmol) in dimethylsulfoxide (85 mL). The resulting mixture was stirred at room temperature for 15 min, poured into a mixture of ice and saturated brine (300 mL), and then extracted with cold ether. The organic layer was washed successively with cold 10% aqueous citric acid solution and cold saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated and hexane was added to the obtained residue to suspend same. Insolubles were collected by filtration to give 6.41 g (90%) of N-tert-butoxycarbonylphenylalaninal. To a suspension of zinc powder (5.59 g, 85.5 mmol) in THF (1 mL) was added dropwise a solution of the above-mentioned N-tert-butoxycarbonylphenylalaninal (6.41 g, 25.7 mmol) and ethyl bromodifluoroacetate (11.1 mL, 85.5 mmol) in THF (16 mL) with ultrasonication. After 3 hr of ultrasonication, dichloromethane (200 mL) and 1N aqueous potassium hydrogensulfate solution (100 mL) were added. The organic layer was separated and dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was separated and purified by silica gel column chromatography (hexane-ethyl acetate, 75:25) to give 2.60 g (27%) of ethyl 4(S)-[(tert-butoxycarbonyl)amino]-2,2-difluoro-3(R)-hydroxy-5-phenylpentanoate as colorless crystals.

Workup

  1. customwith ultrasonication
  2. additionwere added
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated
  6. customthe obtained residue was separated
  7. custompurified by silica gel column chromatography (hexane-ethyl acetate, 75:25)

Sources & evidence

ORD record
ord-d6beec2e8b394cc783778c6b3e4fd9be
Source dataset
uspto-grants-1999_09
Patent number
US05948785

Reaction notes

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