Chlorotrimethylsilane → HCID 58801741, compound

HRID 1670796Notes

Reaction equation

HRID 1670796 reaction equation
BrC(Br)C.C[Si](Cl)(C)C.[Cl:10][C:11]1[C:12]([F:19])=[C:13]([CH:16]=[CH:17][CH:18]=1)[CH2:14]Br.[Br-].ClC1C(F)=C(C=CC=1)C[Zn+].[F:31][C:32]1[CH:41]=[C:40]2[C:35]([C:36](=[O:57])[C:37]([C:52]([O:54][CH2:55][CH3:56])=[O:53])=[CH:38][N:39]2[C@@H:42]([CH:49]([CH3:51])[CH3:50])[CH2:43][O:44][C:45]([O:47][CH3:48])=[O:46])=[CH:34][C:33]=1I.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.[Cl-].[NH4+]>C1COCC1.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[Cl:10][C:11]1[C:12]([F:19])=[C:13]([CH:16]=[CH:17][CH:18]=1)[CH2:14][C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][C:32]=1[F:31])[N:39]([C@@H:42]([CH:49]([CH3:51])[CH3:50])[CH2:43][O:44][C:45]([O:47][CH3:48])=[O:46])[CH:38]=[C:37]([C:52]([O:54][CH2:55][CH3:56])=[O:53])[C:36]2=[O:57]

Participants

11

Reactant 7

HCID 6397ChlorotrimethylsilaneHCID 112011,1-DibromoethaneHCID 25517Ammonium ChlorideHCID 521585Tris(furan-2-yl)phosphaneHCID 5228271-(Bromomethyl)-3-chloro-2-fluorobenzeneHCID 58801777HCID 58801777, compoundHCID 178505940HCID 178505940, compound

Product 1

HCID 58801741HCID 58801741, compound

Reagents, catalysts & solvents 3

HCID 23994ZincCatalyst2×HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
65 °C

Procedure

A solution of dibromoethane (0.01 mL, 0.11 mmol) and 1M TMSCl in THF (0.2 mL, 0.2 mmol) was added to a mixture of Zn (200 mg, 3.06 mmol) in THF (5 mL) at rt and the resulting mixture was heated at 65° C. for 0.5 h. The mixture was then cooled to rt and a solution of 3-chloro-2-fluorobenzyl bromide (700 mg, 3.13 mmol) in THF (10 mL) was added with stirring continuing until all Zn had dissolved (approximately 1.5 hr). To the resulting gray slurry of (3-chloro-2-fluorobenzyl)zinc(II) bromide 18 was added a solution of 17 (1.22 g, 2.4 mmol), Pd(dba)2 (70 mg, 0.12 mmol) and trifurylphosphine (56 mg, 0.24 mmol) in THF (5 mL), and the reaction mixture was stirred at 60° C. for approximately 0.5 h. The mixture was cooled to rt, saturated aqueous ammonium chloride (25 mL) was added to quench the reaction and the mixture was extracted with EtOAc (2×25 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated under reduced pressure to give a brown oil. The crude product was purified on an AnaLogix chromatography system eluting with 33-50% EtOAc/heptanes to give 680 mg (54%, greater than 98% purity) of 19 as a colorless oil.

Workup

  1. temperatureThe mixture was then cooled to rt
  2. dissolutionhad dissolved (approximately 1.5 hr)
  3. stirringthe reaction mixture was stirred at 60° C. for approximately 0.5 h
  4. temperatureThe mixture was cooled to rt
  5. customto quench
  6. customthe reaction
  7. extractionthe mixture was extracted with EtOAc (2×25 mL)
  8. dry with materialThe combined organic phases were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give a brown oil
  12. customThe crude product was purified on an AnaLogix chromatography system
  13. washeluting with 33-50% EtOAc/heptanes

Sources & evidence

ORD record
ord-c5f8b1537f344f459aaa1278db1b70fb
Source dataset
uspto-grants-2011_08
Patent number
US07994194B2

Reaction notes

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