Ethyl bromodifluoroacetate → Ethyl (3R,4S)-4-[[(1,1-dimethylethoxy)carbonyl]amino]-2,2-difluoro-3-hydroxy-6-methylheptanoate

HRID 973924Notes

Reaction equation

HRID 973924 reaction equation
[CH2:1]([O:3][C:4](=[O:9])[C:5](Br)([F:7])[F:6])[CH3:2].[C:10]([NH:17][C@H:18]([CH:23]=[O:24])[CH2:19][CH:20]([CH3:22])[CH3:21])([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11]>O1CCCC1.C(OCC)(=O)C.[Zn]>[CH2:1]([O:3][C:4](=[O:9])[C:5]([F:7])([F:6])[C@H:23]([OH:24])[C@H:18]([CH2:19][CH:20]([CH3:21])[CH3:22])[NH:17][C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])[CH3:2]

Participants

6

Reactant 2

HCID 69585Ethyl bromodifluoroacetateHCID 104275tert-butyl N-[(2S)-4-methyl-1-oxopentan-2-yl]carbamate

Product 1

HCID 13893282Ethyl (3R,4S)-4-[[(1,1-dimethylethoxy)carbonyl]amino]-2,2-difluoro-3-hydroxy-6-methylheptanoate

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1.45 g zinc powder are suspended in 30 ml tetrahydrofuran and heated to reflux temperature. 4.4 g ethylbromodifluoroacetate are added at once and as soon as a vigorous reaction is initiated 2 g of N--BOC--L--leucinal dissolved in 5 ml tetrahydrofuran are added dropwise. After 30 minutes the reaction mixture is allowed to cool, then taken up in ethyl acetate and washed with 2N tartaric acid. The organic phase is dried over magnesium sulfate, evaporated to dryness and chromatographed over silicagel using ether/hexane 2:8 as an eluent. N--BOC--(4S,3R)-2,2-difluorostatine ethyl ester is obtained ([α]D20 =-12.2°, c=0.29 in ethanol).

Workup

  1. temperatureheated
  2. temperatureto reflux temperature
  3. customsoon as a vigorous reaction
  4. additionare added dropwise
  5. temperatureto cool
  6. washwashed with 2N tartaric acid
  7. dry with materialThe organic phase is dried over magnesium sulfate
  8. customevaporated to dryness
  9. customchromatographed

Sources & evidence

ORD record
ord-32fac99628004f62a81b7dd7d4b1f023
Source dataset
uspto-grants-1991_11
Patent number
US05066643

Reaction notes

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