2-Methyl-3-buten-2-ol → HCID 54169282, compound

HRID 975135Notes

Reaction equation

HRID 975135 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH3:17].[CH3:18][C:19]([OH:23])([CH:21]=[CH2:22])[CH3:20].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[OH:23][C:19]([CH3:20])([CH3:18])[CH:21]=[CH:22][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH3:17]

Participants

7

Reactant 4

HCID 82572-Methyl-3-buten-2-olHCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 11185464(R)-5-Bromo-3-(1-methyl-2-pyrrolidinyl methyl)-1H-indole

Product 1

HCID 54169282HCID 54169282, compoundYield 25.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Procedure

A stirred solution of 5-bromo-3-(N-methyl-2(R)-pyrrolidinylmethyl)-1H-indole (WO-A-92/06973; 879 mg, 3.0 mmol), 2-methylbut-3-en-2-ol (0.408 ml, 3.9 mmol), tri-o-tolylphosphine (273 mg, 0.90 mmol), palladium(II) acetate (45 mg, 0.20 mmol), triethylamine (0.84 ml, 6.0 mmol) and acetonitrile (50 ml), under nitrogen, was heated under reflux for 24 hours, allowed to cool, then partitioned between ethyl acetate and 2M aqueous sodium carbonate solution. The organic phase was separated, washed sequentially with 2M aqueous sodium carbonate solution (×2) and brine (×1), dried (Na2SO4) and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel, eluting with a solvent gradient of 0.880 aqueous ammonia:methanol: dichloromethane (0:5:95 to 0.5:5:95), to afford the title compound as a solid (226 mg), m.p. 155°-158° C. Rf 0.10 (SS 1). [α]D25 +81° (c=0.1, CH3OH). Found: C,75.27; H,8.96; N,8.99. C19H26N2O; 0.25 H2O requires C,75.33; H,8.82; N,9.25%.

Workup

  1. temperatureunder reflux for 24 hours
  2. temperatureto cool
  3. custompartitioned between ethyl acetate and 2M aqueous sodium carbonate solution
  4. customThe organic phase was separated
  5. washwashed sequentially with 2M aqueous sodium carbonate solution (×2) and brine (×1)
  6. dry with materialdried (Na2SO4)
  7. customevaporated under reduced pressure
  8. customThe crude product was purified by column chromatography on silica gel
  9. washeluting with a solvent gradient of 0.880 aqueous ammonia:methanol: dichloromethane (0:5:95 to 0.5:5:95)

Sources & evidence

ORD record
ord-1985b3e6b8cf496f95e179d0a7c0e8d8
Source dataset
uspto-grants-1997_03
Patent number
US05607960

Reaction notes

Loading…