Allyl bromide → HCID 59853567, compound

HRID 1177029Notes

Reaction equation

HRID 1177029 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:14])([F:13])[CH2:10][CH:9]1[C:15]([OH:17])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:18](Br)[CH:19]=[CH2:20]>C(=O)(O)[O-].[Na+].[Cl-].C([N+](CCCCCCCC)(CCCCCCCC)C)CCCCCCC.ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:13])([F:14])[CH2:10][CH:9]1[C:15]([O:17][CH2:20][CH:19]=[CH2:18])=[O:16])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 2

HCID 7841Allyl bromideHCID 235125141-((Tert-butoxy)carbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid

Product 1

HCID 59853567HCID 59853567, compoundYield 74.5%

Reagents, catalysts & solvents 3

HCID 21218Trioctylmethylammonium chlorideCatalystHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
25 °C

Procedure

4,4-Difluoro-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (Example 14b, 6.77 g, 26.96 mmol) was dissolved in a 5% aqueous sodium bicarbonate solution (50 mL). Allyl bromide (3.26 g, 26.96 mmol) and trioctylmethylammonium chloride (“Aliquat 336”, 10.90 g, 26.97 mmol) were dissolved in dichloromethane (50 mL) and were added to the aqueous solution. The biphasic reaction mixture was stirred vigorously for 48 h at 25° C. The layers were separated and the aqueous layer was extracted with dichloromethane (3×70 mL). The combined organic layers were dried over sodium sulfate and filtered. The solvent was removed in vacuo to afford the crude desired product, which was purified by flash column chromatography (Merck silica gel 60, 40-63 μm, 20% ethyl acetate in hexanes) to afford the desired product, 4,4-difluoro-pyrrolidine-1,2-dicarboxylic acid 2-allyl ester 1-tert-butyl ester (5.85 g, 20.09 mmol, 74.5% yield) as a clear, slightly yellowish oil. 1H NMR (400 MHz, CDCl3) δ: 1.44 (9H, s), 2.43-2.54 (1H, m), 2.64-2.80 (1H, m), 3.78-3.94 (2H, m), 4.46-4.73 (3H, m), 5.24-5.37 (2H, m), 5.87-5.96 (1H, m).

Workup

  1. additionwere added to the aqueous solution
  2. customThe biphasic reaction mixture
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with dichloromethane (3×70 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed in vacuo
  8. customto afford the crude desired product, which
  9. customwas purified by flash column chromatography (Merck silica gel 60, 40-63 μm, 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e9875e3a770a49d89e148a97e947cadf
Source dataset
uspto-grants-2010_11
Patent number
US07842838B2

Reaction notes

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