Chlorotrimethylsilane → Ethyl 3-(cyclopentylamino)-2,2-difluoropropanoate

HRID 2111264Notes

Reaction equation

HRID 2111264 reaction equation
Cl[Si](C)(C)C.Br[C:7]([F:14])([F:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9].N1([CH2:24][NH:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)C2C=CC=CC=2N=N1>O1CCCC1.[Zn]>[CH2:11]([O:10][C:8](=[O:9])[C:7]([F:14])([F:13])[CH2:24][NH:25][CH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1)[CH3:12]

Participants

6

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 69585Ethyl bromodifluoroacetateHCID 5235843N-(benzotriazol-1-ylmethyl)cyclopentanamine

Product 1

HCID 57634998Ethyl 3-(cyclopentylamino)-2,2-difluoropropanoateYield 39.1%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 4.3 g (0.066 g-atom) of zinc powder in 40 mL of tetrahydrofuran was added 4.1 mL (0.032 mole) of chlorotrimethylsilane. After stirring for 10 minutes, 6.6 g (0.032 mole) of ethyl bromodifluoroacetate was added dropwise at room temperature. After 10 minutes, a solution of 7.0 g (0.032 mole) of benzotriazol-1-ylmethyl-cyclopentyl-amine in tetrahydrofuran was added dropwise. The reaction mixture was stirred at room temperature for 3 hours and then quenched by the addition of saturated aqueous sodium carbonate. The mixture was filtered through Celite. The filtrate was extracted twice with ether. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was distilled under vacuum to give 2.77 g of 3-cyclopentylamino-2,2-difluoro-propanoic acid ethyl ester as a colorless oil. bp 75-82 degrees at 10 mm Hg.

Workup

  1. waitAfter 10 minutes
  2. stirringThe reaction mixture was stirred at room temperature for 3 hours
  3. customquenched by the addition of saturated aqueous sodium carbonate
  4. filtrationThe mixture was filtered through Celite
  5. extractionThe filtrate was extracted twice with ether
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. distillationThe residue was distilled under vacuum

Sources & evidence

ORD record
ord-f1d62c4cb33a45fa9c8444ae364a2166
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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