4-Bromobutyryl chloride → HCID 57447681, compound

HRID 661601Notes

Reaction equation

HRID 661601 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([C@@H:11]([OH:21])[C@H:12]([NH:15][C:16]([CH:18]([Cl:20])[Cl:19])=[O:17])[CH2:13][F:14])=[CH:9][CH:10]=1)(=[O:4])=[O:3].C(N(C(C)C)CC)(C)C.[Br:31][CH2:32][CH2:33][CH2:34][C:35](Cl)=[O:36]>O1CCCC1.C(OCC)(=O)C>[Cl:19][CH:18]([Cl:20])[C:16]([NH:15][CH:12]([CH2:13][F:14])[CH:11]([O:21][C:35](=[O:36])[CH2:34][CH2:33][CH2:32][Br:31])[C:8]1[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:10][CH:9]=1)=[O:17]

Participants

6

Reactant 3

HCID 702254-Bromobutyryl chlorideHCID 81531DiisopropylethylamineHCID 114811Florfenicol

Product 1

HCID 57447681HCID 57447681, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Upon stirring a mixture of florfenicol (8.8 g, 1 equivalent), diisopropylethylamine (5 mL, 1.2 equivalents), and 4-N,N-dimethylaminopyridine (1.2 g, 0.4 equivalent) in tetrahydrofuran (90 mL) at −20° C., a solution of 4-bromobutyryl chloride (5 g, 1.1 equivalent) in tetrahydrofuran (15 mL) was added via a syringe. The solution was stirred at room temperature under a nitrogen atmosphere overnight and diluted with ethyl acetate. The resulting solution was washed with 1 M HCl(aq) and the organic layer was separated and concentrated to give a brown oil. The crude oil was purified by gel column chromatography to give 4-bromo-butyric acid 2-(2,2-dichloro-acetyl amino)-3-fluoro-1-(4-methanesulfonyl-phenyl)-propyl ester (5.6 g, 45% yield) as a brown foam; H1-NMR (DMSO-d6), δ=2.1 ppm (p, 2H), 2.6 ppm (t, 2H), 3.2 ppm (s, 3H), 3.5 ppm (t, 2H), 4.2-4.6 (m, 3H), 6.0 ppm (d, 1H), 6.4 ppm (s, 1H), 7.6 ppm (d, 2H), 7.9 ppm (d, 2H), 8.9 ppm (d, 2H).

Workup

  1. stirringThe solution was stirred at room temperature under a nitrogen atmosphere overnight
  2. washThe resulting solution was washed with 1 M HCl(aq)
  3. customthe organic layer was separated
  4. concentrationconcentrated
  5. customto give a brown oil
  6. customThe crude oil was purified by gel column chromatography

Sources & evidence

ORD record
ord-dccbaca20050404bb70ce110350bb4ee
Source dataset
uspto-grants-2011_12
Patent number
US08084643B2

Reaction notes

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