Triphenylphosphine → (R)-2-[2-bromo-4-fluoro-6-(prop-1-enyl)phenoxy]but-3-enyl 4-methylbenzenesulfonate

HRID 902315Notes

Reaction equation

HRID 902315 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([CH:9]=[CH:10][CH3:11])[C:3]=1[OH:12].O[C@@H:14]([CH:27]=[CH2:28])[CH2:15][O:16][S:17]([C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=1)(=[O:19])=[O:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[CH3:26][C:23]1[CH:24]=[CH:25][C:20]([S:17]([O:16][CH2:15][C@H:14]([O:12][C:3]2[C:4]([CH:9]=[CH:10][CH3:11])=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[Br:1])[CH:27]=[CH2:28])(=[O:19])=[O:18])=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 7015761(S)-3-Butene-1,2-diol-1-(p-toluenesulfonate)HCID 691167852-Bromo-4-fluoro-6-(prop-1-enyl)phenol

Product 1

HCID 86609112(R)-2-[2-bromo-4-fluoro-6-(prop-1-enyl)phenoxy]but-3-enyl 4-methylbenzenesulfonateYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-bromo-4-fluoro-6-(prop-1-enyl)phenol, prepared in Example 37, step 4 (4.5 g, 0.019 mol) and (S)-toluene-4-sulfonic acid 2-hydroxy-but-3-enyl ester (7.07 g, 0.028 mol) and triphenylphosphine (11.22 g, 0.043 mol) in anhydrous THF (200 mL) at room temperature was added diethyl azodicarboxylate (7.7 mL, 0.047 mol) then the reaction mixture stirred at room temperature for 19 hours. The reaction was quenched by the addition of water (100 mL), stirred vigorously for 5 minutes and the resulting oily suspension extracted with methylene chloride (300 mL). The organic phase was separated, washed with water (2×100 mL), and saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford a yellow oil. Purification by flash chromatography using a solvent gradient of 0 to 20% ethyl acetate in hexane gave 7.26 g (82%) of (R)-2-[2-bromo-4-fluoro-6-(prop-1-enyl)phenoxy]but-3-enyl 4-methylbenzenesulfonate as a colorless oil. MS (ES) m/z 472.1 ([M+NH4]+).

Workup

  1. customThe reaction was quenched by the addition of water (100 mL)
  2. stirringstirred vigorously for 5 minutes
  3. extractionthe resulting oily suspension extracted with methylene chloride (300 mL)
  4. customThe organic phase was separated
  5. washwashed with water (2×100 mL), and saturated brine (100 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto afford a yellow oil
  10. customPurification by flash chromatography

Sources & evidence

ORD record
ord-eb566c39d7604a188aefb9c85ac2dc86
Source dataset
uspto-grants-2008_04
Patent number
US07365095B2

Reaction notes

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