Chlorotrimethylsilane → HCID 58920561, compound

HRID 1365484Notes

Reaction equation

HRID 1365484 reaction equation
[F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:5]=[C:6](Br)[CH:7]=[CH:8][CH:9]=1.[Li]CCCC.[C:18]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1)#[N:19].C[Si](C)(C)[Cl:28].[CH2:31]([Mg]Cl)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CCOCC.C1COCC1>[Cl:28][C:23]1[CH:24]=[CH:25][C:20]([C:18]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([O:3][C:2]([F:12])([F:11])[F:1])[CH:5]=2)([NH2:19])[CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[N:21][CH:22]=1

Participants

8

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 7522Pyridine-2-carbonitrileHCID 5199641-Bromo-3-(trifluoromethoxy)benzeneHCID 178418336HCID 178418336, compoundHCID 178418339Butyllithium

Product 1

HCID 58920561HCID 58920561, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A dry 250 mL pear-shaped flask was equipped with a stir bar and fitted to an adapter connected to the vacuum line. The flask was dried with a heat gun under vacuum, cooled and then purged several times with nitrogen. Under a stream of nitrogen, 3-(trifluoromethoxy)bromobenzene (5.2 g, 21.5 mmoles) was added to the flask and dissolved in anhydrous ether (120 mL). The flask was fitted with a septum which was connected to the nitrogen line via a 16 gauge 1½ PrecisionGlide® needle. The stirring solution was cooled to −78° C. for 10 minutes, n-BuLi (1.6M in hexanes, 13.5 mL. 21.5 mmoles) was added drop wise. After 15 minutes, a solution of 2-cyanopyridine (2.99 g, 21.5 mmoles) in anhydrous THF (20 mL) was added from a syringe. The reaction was stirred for 2 hours at −78° C. and trimethylchlorosilane (2.73 mL, 21.5 mmoles) was added. The reaction vessel was removed from the acetone/dry ice bath and the reaction was allowed to warm up to room temperature. After 30 minutes, the reaction vessel was cooled to −78° C., Benzylmagnesium chloride (2.0M in THF, 10.75 mL, 21.5 mmoles) was added and the reaction was allowed to slowly warm to room temperature. The reaction was quenched with H2O (50 mL). The crude product was poured into 200 mL ethyl acetate in a 1000 mL separatory funnel. The light brown solution was washed with saturated aqueous NH4Cl (3×100 mL), then with water (2×100 mL). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified by column chromatography on a silica gel ISCO with 100-90% hexanes in ethylacetate to yield 1-(5-chloropyridin-2-yl)-2-phenyl-1-(3-(trifluoromethoxy)phenyl)ethanamine 3.63 g (43% yield). LC-MS (methanol) [M+1]=393 1H NMR (CDCl3) δ1.85 (broad s, 2H), δ 3.49 (d, J=13.20, 1 H), δ 3.87 (d, J=13.20, 1 H), δ6.78-6.80 (d, 2 H), δ 7.08 (d, 1 H) δ 7.12-7.42 (m, 7 H), δ7.58-7.56 (dd, 1 H), δ 8.55 (d, 1 H).

Workup

  1. customA dry 250 mL pear-shaped flask was equipped with a stir bar
  2. customfitted to an adapter
  3. customThe flask was dried with a heat gun under vacuum
  4. temperaturecooled
  5. custompurged several times with nitrogen
  6. customThe flask was fitted with a septum which
  7. customThe reaction vessel was removed from the acetone/dry ice bath
  8. temperatureto warm up to room temperature
  9. waitAfter 30 minutes
  10. temperaturethe reaction vessel was cooled to −78° C.
  11. temperatureto slowly warm to room temperature
  12. customThe reaction was quenched with H2O (50 mL)
  13. additionThe crude product was poured into 200 mL ethyl acetate in a 1000 mL separatory funnel
  14. washThe light brown solution was washed with saturated aqueous NH4Cl (3×100 mL)
  15. dry with materialThe organic layer was dried over MgSO4
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo
  18. customThe crude residue was purified by column chromatography on a silica gel ISCO with 100-90% hexanes in ethylacetate

Sources & evidence

ORD record
ord-498aaf5a91e54c00ba7b32478934d4aa
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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