1-Bromo-2-fluorobenzene → 1-(2-Fluorophenyl)-2-(1,1,1-trifluorobut-3-en-2-yloxy)ethanone

HRID 2045875Notes

Reaction equation

HRID 2045875 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[F:8].C([Li])CCC.CON(C)[C:17](=[O:27])[CH2:18][O:19][CH:20]([CH:25]=[CH2:26])[C:21]([F:24])([F:23])[F:22]>C1COCC1>[F:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:17](=[O:27])[CH2:18][O:19][CH:20]([CH:25]=[CH2:26])[C:21]([F:23])([F:22])[F:24]

Participants

5

Reactant 3

HCID 612591-Bromo-2-fluorobenzeneHCID 86668366N-Methoxy-N-methyl-2-(1,1,1-trifluorobut-3-en-2-yloxy)acetamideHCID 178418339Butyllithium

Product 1

HCID 668689851-(2-Fluorophenyl)-2-(1,1,1-trifluorobut-3-en-2-yloxy)ethanoneYield 91.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution 1-bromo-2-fluorobenzene (0.967 kg, 5.527 mol) in THF (6.2 L) at −75° C., was added n-butyllithium (2.50 M in hexane, 2.09 L, 5.22 mol) while maintaining temperature below −65° C. (ca. 100 min.). After 15 mins, a solution of N-methoxy-N-methyl-2-(1,1,1-trifluorobut-3-en-2-yloxy)acetamide (0.949 kg, 4.178 mol) in THF (1.6 L) was added while maintaining temperature below −65° C. (ca. 70 min.). After 2.5 h at −78° C., the reaction was quenched by addition of sat. aq. NH4Cl (3.0 L) and methyl tert-butyl ether (9.0 L). The reaction mixture was warmed to rt, the aq. phase was extracted again with methyl tert-butyl ether (2.5 L). The organic phases were combined, washed with sat. aq. NaCl (2×0.3 L) and concentrated under vacuum to afford the title compound as an oil (1.007 kg, 80.0%). 1H NMR (500 MHz, CDCl3) δ ppm 7.96 (td, J=7.6, 1.8 Hz, 1H), 7.62-7.54 (m, 1H), 7.33-7.25 (m, 1H), 7.20-7.12 (m, 1H), 5.86 (ddd, J=17.5, 10.4, 7.3 Hz, 1H), 5.60 (dd, J=20.5, 13.8 Hz, 2H), 4.91-4.76 (m, 2H), 4.39 (dq, J=12.8, 6.4 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ ppm 193.55, 162.14 (d, JCF=254.1 Hz), 135.36 (d, JCF=9.2 Hz), 130.62 (d, JCF=3.2 Hz), 128.49, 124.85 (d, JCF=3.3 Hz), 123.89, 122.93, 122.72 (d, JCF=24.5 Hz), 116.50 (d, JCF=23.7 Hz), 78.97 (q, JCF=31.4 Hz), 74.56 (d, JCF=12.4 Hz).

Workup

  1. temperaturewhile maintaining temperature below −65° C. (ca. 100 min.)
  2. temperaturewhile maintaining temperature below −65° C. (ca. 70 min.)
  3. waitAfter 2.5 h at −78° C.
  4. customthe reaction was quenched by addition of sat. aq. NH4Cl (3.0 L) and methyl tert-butyl ether (9.0 L)
  5. extractionthe aq. phase was extracted again with methyl tert-butyl ether (2.5 L)
  6. washwashed with sat. aq. NaCl (2×0.3 L)
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-03a623c4e75c4837a9e0fe68e1883248
Source dataset
uspto-grants-2013_11
Patent number
US08592408B2

Reaction notes

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