2-Bromothioanisole → HCID 69410336, compound

HRID 1592706Notes

Reaction equation

HRID 1592706 reaction equation
BrC1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]C.[CH3:10][C@@H:11]1[CH2:16][NH:15][CH2:14][CH2:13][NH:12]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>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].C1(C)C=CC=CC=1>[CH3:10][C@H:11]1[NH:12][CH2:13][CH2:14][N:15]([C:5]2[CH:4]=[CH:3][S:8][C:6]=2[CH3:7])[CH2:16]1

Participants

7

Reactant 4

HCID 881662-BromothioanisoleHCID 634876Binap, (A+-)-HCID 73304342-Methylpiperazine, (R)-HCID 23676156Sodium t-butoxide

Product 1

HCID 69410336HCID 69410336, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

2-Bromothioanisole (300 mg, 1.48 mmol), (R)-2-methylpiperazine (185 mg, 1.85 mmol), Pd2(dba)3 (32 mg, 0.35 mmol), BINAP (41 mg, 0.66 mmol), sodium t-butoxide (200 mg, 2.08 mmol) and anhydrous toluene (3 ml) were combined in a 15 ml round-bottomed flask. The atmosphere in the flask was evacuated and flushed with nitrogen (3×). The mixture was lowered into an oil bath heated to 100° C. After heating for about 1.2 hours, the mixture was cooled, diluted with ethyl acetate (100 ml), filtered through Celite, and concentrated to a crude oil (285 mg). The oil was loaded onto an cation exchange column, and the column was flushed with methanol (100 ml), and then with 2 M ammonia/methanol (100 ml). The basic methanol solution was concentrated to an oil (250 mg). The oil was further purified by flash chromatography using 19:1 dichloromethane: 0.5 M ammonia/methanol as eluent to yield the final product (160 mg, 58%) as an oil. LRMS (ESI+): 223.0 (M+1)

Workup

  1. customThe atmosphere in the flask was evacuated
  2. customflushed with nitrogen (3×)
  3. customThe mixture was lowered into an oil bath
  4. temperatureAfter heating for about 1.2 hours
  5. temperaturethe mixture was cooled
  6. additiondiluted with ethyl acetate (100 ml)
  7. filtrationfiltered through Celite
  8. concentrationconcentrated to a crude oil (285 mg)
  9. customthe column was flushed with methanol (100 ml)
  10. concentrationThe basic methanol solution was concentrated to an oil (250 mg)
  11. customThe oil was further purified by flash chromatography

Sources & evidence

ORD record
ord-361aead7738340569786f97c1f1a3410
Source dataset
uspto-grants-2007_11
Patent number
US07291619B2

Reaction notes

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