Triphenylphosphine → (3S)-1-(2-pyridinylmethyl)-3-piperidinyl (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylate

HRID 841932ノート

反応式

HRID 841932 の反応式
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([OH:14])[CH2:9]1.[O:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]1[C:30](O)=[O:31].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[O:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C@H:25]1[C:30]([O:14][C@H:10]1[CH2:11][CH2:12][CH2:13][N:8]([CH2:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH2:9]1)=[O:31]

参加物

6

反応物 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 12050655(2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylic acidHCID 53657319(R)-1-(pyridin-2-ylmethyl)piperidin-3-ol

生成物 1

HCID 57262118(3S)-1-(2-pyridinylmethyl)-3-piperidinyl (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylate収率 54.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

(3R)-1-(2-Pyridinylmethyl)-3-piperidinol (117 mg) [see Preparation 35] was added to a stirred solution of (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylic acid (150 mg) [see Preparation 3], triphenylphosphine (192 mg) and diethyl azodicarboxylate (0.115 ml) in dry tetrahydrofuran (6 ml). The reaction mixture was stirred at reflux for 16 hours, after which time the solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and 0.5M aqueous hydrochloric acid. The aqueous layer was then basified with 15% sodium hydroxide and the product extracted with ethyl acetate. The organic layer was then separated, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with 98:2, by volume, ethyl acetate:methanol to afford (3S)-1-(2-pyridinylmethyl)-3-piperidinyl (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylate (140 mg) as a yellow oil. The hydrochloride salt was prepared by dissolving the title compound in ethyl acetate and bubbling hydrogen chloride gas through the solution, to afford the title compound as a white solid.

後処理

  1. temperatureat reflux for 16 hours
  2. customafter which time the solvent was removed under reduced pressure
  3. customthe residue partitioned between ethyl acetate and 0.5M aqueous hydrochloric acid
  4. extractionthe product extracted with ethyl acetate
  5. customThe organic layer was then separated
  6. dry with materialdried over magnesium sulphate
  7. customthe solvent removed under reduced pressure
  8. customThe crude product was purified by column chromatography on silica gel eluting with 98:2, by volume, ethyl acetate

出典と根拠

ORDレコード
ord-1cf717aad66e4fc6814e6a137ee799db
出典データセット
uspto-grants-2002_04
特許番号
US06372736B1

反応ノート

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