Phosphorus sulfide (P2S5) → [2-(4-Bromo-2-fluoro-benzylthiocarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid ethyl ester

HRID 457974Notes

Reaction equation

HRID 457974 reaction equation
[CH2:1]([O:3][C:4](=[O:27])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([CH3:14])=[CH:9][C:8]=1[C:15](=O)[NH:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:19]=1[F:25])[CH3:2].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:29]>N1C=CC=CC=1.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:27])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([CH3:14])=[CH:9][C:8]=1[C:15](=[S:29])[NH:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:19]=1[F:25])[CH3:2]

Participants

5

Reactant 2

HCID 14817Phosphorus sulfide (P2S5)HCID 22093479(2-(4-Bromo-2-fluoro-benzylcarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid ethyl ester

Product 1

HCID 22093484[2-(4-Bromo-2-fluoro-benzylthiocarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid ethyl esterYield 177.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

A stirring solution of [2-(4-bromo-2-fluoro-benzylcarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid ethyl ester (0.816 g, 1.83 mmol) in pyridine (3.7 mL, 0.5 M) was treated with phosphorus pentasulfide (0.41 g, 0.92 mmol) and heated to 115° C. for 3 h. The reaction was allowed to cool to room temperature, diluted with ethyl acetate and successively washed with 1 M HCl and saturated aq NaCl. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting brown oil was dissolved in a minimal amount of methylene chloride and flushed through a plug of silica using 40% ethyl acetate in heptane as the eluant. The filtrate was concentrated to afford [2-(4-bromo-2-fluoro-benzylthiocarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid ethyl ester (0.75 g, 89%) as a yellow solid: mp 98–100° C.; Rf 0.45 (30% ethyl acetate in heptane); 1H NMR (CDCl3, 300 mHz) δ 10.15 (bs, 1H), 8.26 (d, J=8.4 Hz, 1 H), 7.38 (t, J=8.4 Hz, 1 H), 7.26–7.23 (m, 2 H), 6.53 (d, J=10.8 Hz, 1 H), 5.08 (d, J=5.4 Hz, 2 H), 4.67 (s, 3 H), 4.20 (q, J=7.2 Hz, 2 H), 2.23 (s, 2 H), 1.27 (dt, J1=6.8 Hz, J2=0.6 Hz, 3 H).

Workup

  1. temperatureto cool to room temperature
  2. washsuccessively washed with 1 M HCl and saturated aq NaCl
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting brown oil was dissolved in a minimal amount of methylene chloride
  7. customflushed through a plug of silica using 40% ethyl acetate in heptane as the eluant
  8. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-9ea3974cc4204096bf65815a05c003cc
Source dataset
uspto-grants-2007_03
Patent number
US07189749B2

Reaction notes

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