Ammonium Chloride → AC1LGF1F

HRID 337280Notes

Reaction equation

HRID 337280 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[CH3:13])=[CH:4][N:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[Li+].C[Si]([N-:44][Si](C)(C)C)(C)C.[NH4+].[Cl-]>CCOC(C)=O.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1>[CH3:13][N:9]1[CH2:10][CH2:11][CH2:12][C@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([NH2:44])=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 106317716-Chloronicotine

Product 1

HCID 769989AC1LGF1FYield 100%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

In a 75 mL sealed tube, (S)-2-chloro-5-(1-methylpyrrolidin-2-yl)pyridine (622 mg, 3.16 mmol) and 2-(dicyclohexylphosphino)biphenyl (222 mg, 633 μmol) were combined with THF (15 ml) to give a light yellow solution. The solution was degassed with argon. Tris(dibenzylideneacetone)dipalladium (0) (290 mg, 316 μmol) was added. LiHMDS (9.49 ml of 1M solution in THF, 9.49 mmol) was added. The reaction was placed under an argon atmosphere and sealed. The reaction mixture was heated to 90° C. and stirred for 15 h. The reaction was complete by tlc. The reaction mixture was cooled to room temperature and diluted with EtOAc. The reaction mixture was poured into 150 mL sat NH4Cl and extracted with EtOAc (4×75 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography with stepwise gradient (silica gel, 40 g, 10% to 50% (60:10:1 CH2Cl2:methanol: NH4OH)/CH2Cl2) gradient to afford the desired product (560 mg, 99%). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.57-2.03 (m, 3 H) 2.04-2.39 (m and overlapping s, 5 H) 2.92 (t, J=8.12 Hz, 1 H) 3.14-3.29 (m, 1 H) 4.40 (br. s., 2 H) 6.51 (d, J=8.69 Hz, 1 H) 7.47 (dd, J=8.31, 2.27 Hz, 1 H) 7.95 (d, J=2.27 Hz, 1 H)

Workup

  1. customIn a 75 mL sealed tube
  2. customto give a light yellow solution
  3. customThe solution was degassed with argon
  4. customsealed
  5. temperatureThe reaction mixture was cooled to room temperature
  6. additionThe reaction mixture was poured into 150 mL
  7. extractionextracted with EtOAc (4×75 mL)
  8. dry with materialThe organic layers were dried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by flash chromatography with stepwise gradient (silica gel, 40 g, 10% to 50% (60:10:1 CH2Cl2:methanol: NH4OH)/CH2Cl2) gradient

Sources & evidence

ORD record
ord-5fde7ae932fb401eafc364940fa67acb
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

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