Triethylamine → 3-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]ethynyl-3-piperidinol

HRID 2216372

反応式

HRID 2216372 の反応式
[CH2:1]([C:8]1[C:13](I)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@H:17]([OH:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC([N:30]1[CH2:35][CH2:34][CH2:33][C:32]([C:37]#[CH:38])([OH:36])[CH2:31]1)=O)(C)(C)C.C(N(CC)CC)C.[Cl-].N>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I.C(OCC)(=O)C.O.CN(C)C=O.CO>[CH2:1]([C:8]1[C:13]([C:38]#[C:37][C:32]2([OH:36])[CH2:33][CH2:34][CH2:35][NH:30][CH2:31]2)=[CH:12][CH:11]=[C:10]([N:15]2[CH2:19][C@@H:18]([O:20][CH3:21])[C@H:17]([OH:22])[CH2:16]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

11

反応物 4

HCID 8471TriethylamineHCID 113843072-Benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]pyridineHCID 20976574Ammonia chlorideHCID 219422481-Boc-3-ethynyl-3-hydroxypiperidine

生成物 1

HCID 98015133-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]ethynyl-3-piperidinol収率 86.6%

試薬・触媒・溶媒 6

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of 450 mg of 2-benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1yl]-pyridine (Production Example 1), 272 mg of 1-tert-butoxycarbonyl-3-ethynyl-3-piperidinol (Production Example 15), 63.6 mg of tetrakis(triphenylphosphine)palladium (0), 41.9 mg of copper (I) iodide, 460 μl of triethylamine, 5 ml of methanol and 1 ml of N,N-dimethyl formamide was heated under reflux under nitrogen atmosphere for 3 hours. After standing to cool, water, ethyl acetate, an aqueous ammonia chloride solution were added to the reaction mixture, and the organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and then the solvent was removed. To the residue were added 2 ml of trifluoroacetic acid and 2 ml of dichloromethane, followed by stirring at room temperature for 1 hour. The reaction mixture was neutralized with an aqueous sodium hydrogen carbonate solution and an organic layer was separated by adding ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and the solvent was removed. The residue was purified by NH-silica gel column chromatography with 5% methanol/ethyl acetate, to give 387 mg of the entitled compound.

後処理

  1. temperaturewas heated
  2. temperatureunder reflux under nitrogen atmosphere for 3 hours
  3. temperatureto cool
  4. washthe organic layer was washed with water and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed
  7. additionTo the residue were added 2 ml of trifluoroacetic acid and 2 ml of dichloromethane
  8. customan organic layer was separated
  9. additionby adding ethyl acetate
  10. washThe organic layer was washed with brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customthe solvent was removed
  13. customThe residue was purified by NH-silica gel column chromatography with 5% methanol/ethyl acetate

出典と根拠

ORDレコード
ord-80ac6040bb384acbabcb253af20def6e
出典データセット
uspto-grants-2006_09
特許番号
US07112593B2

関連ノート

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