Ethyl bromodifluoroacetate → HCID 121324404, compound

HRID 527326Notes

Reaction equation

HRID 527326 reaction equation
[F:1][CH:2]([F:18])[C:3](=[N:11][S@@:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[F:10].Br[C:20]([F:27])([F:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22].C([Zn]CC)C>C1COCC1>[C:14]([S@:12]([NH:11][C@@:3]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[F:10])([CH:2]([F:18])[F:1])[C:20]([F:27])([F:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22])=[O:13])([CH3:17])([CH3:15])[CH3:16]

Participants

5

Reactant 3

HCID 69585Ethyl bromodifluoroacetateHCID 121317072HCID 121317072, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 121324404HCID 121324404, compoundYield 63.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (R)—N-(2,2-difluoro-1-(2-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide (4.60 g, 16.6 mmol), ethyl 2-bromo-2,2-difluoro-acetate (6.73 g, 33.18 mmol) and Rh(PPh3)3C1 (469 mg, 498 μmol) in THF (90 mL) was added a solution of diethyl zinc (1 M in THF, 33 mL) dropwise at −78° C. over a period of 20 minutes under Ar, during which the temperature was maintained below −65° C. The reaction mixture was warmed to 0° C. over a period of 10 minutes and stirred at 0° C. for 2 hours. TLC (petroleum ether/ethyl acetate=3:1) showed the starting material was consumed completely. The dark red solution was quenched by water (40 mL) and then filtered. The filtrate was extracted with ethyl acetate (100 mL, twice). The combined organic phases were washed with saturated brine (30 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (petroleum ether/ethyl acetate=4:1) to give ethyl (S)-3-(((R)-tert-butylsulfinyl)amino)-2,2,4,4-tetrafluoro-3-(2-fluorophenyl)butanoate (4.26 g, 62.1% yield). 1H NMR (DMSO-d6, 400 MHz): δ 7.65-7.31 (m, 1H), 7.49-7.44 (m, 1H), 7.23-7.12 (m, 2H), 6.93-6.66 (m, 1H), 5.00 (s, 1H), 4.39-4.29 (m, 2H), 1.39 (s, 9H), 1.32 (t, J=8.0 Hz, 3H).

Workup

  1. temperatureduring which the temperature was maintained below −65° C
  2. customwas consumed completely
  3. customThe dark red solution was quenched by water (40 mL)
  4. filtrationfiltered
  5. extractionThe filtrate was extracted with ethyl acetate (100 mL
  6. washThe combined organic phases were washed with saturated brine (30 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by column chromatography on silica gel (petroleum ether/ethyl acetate=4:1)

Sources & evidence

ORD record
ord-024bc1b541074d2a8ebd5784a062d03e
Source dataset
uspto-grants-2016_05
Patent number
US09346797B1

Reaction notes

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