Triphenylphosphine → (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-(pyridin-2-yloxy)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

HRID 132958ノート

反応式

HRID 132958 の反応式
[C:1]([NH:4][C@:5]1([C@@H:54]([CH2:56][CH3:57])[CH3:55])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:45][CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C:11]([NH:13][C@@H:14]([CH2:36][C:37]2[CH:42]=[C:41]([F:43])[CH:40]=[C:39]([F:44])[CH:38]=2)[C@@H:15]([C@H:17]2CCCC[N:18]2[CH:23](C2C=CC=CC=2)[C:24]2[CH:29]=CC=CC=2)[OH:16])=[O:12])[C:6]1=[O:53])(=[O:3])[CH3:2].FC1C=C(C=C(F)C=1)C[C@H]1[C@@H]([C@H]2C[C@@H]([O:73][C:74]3[CH:79]=[CH:78][CH:77]=[CH:76][N:75]=3)CN2C(C2C=CC=CC=2)C2C=CC=CC=2)OC(=O)N1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.FC1C=C(C=C(F)C=1)C[C@H]1[C@@H]([C@H]2C[C@H](O)CN2C(C2C=CC=CC=2)C2C=CC=CC=2)OC(=O)N1.OC1C=CC=CN=1>C1COCC1>[C:1]([NH:4][C@:5]1([C@@H:54]([CH2:56][CH3:57])[CH3:55])[CH2:9][CH2:8][N:7]([C@@H:10]([CH2:45][CH2:46][C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:11]([NH:13][C@@H:14]([CH2:36][C:37]2[CH:38]=[C:39]([F:44])[CH:40]=[C:41]([F:43])[CH:42]=2)[C@H:15]([OH:16])[C@H:17]2[CH2:29][C@@H:24]([O:73][C:74]3[CH:79]=[CH:78][CH:77]=[CH:76][N:75]=3)[CH2:23][NH:18]2)=[O:12])[C:6]1=[O:53])(=[O:3])[CH3:2]

参加物

8

反応物 6

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 58608198(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-oneHCID 69194179(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1S,2S)-1-((R)-1-benzhydrylpiperidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamideHCID 69194209(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)oxazolidin-2-oneHCID 178516071HCID 178516071、化合物

生成物 1

HCID 69195856(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-(pyridin-2-yloxy)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Step 12 (A): (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)oxazolidin-2-one. To a solution of triphenylphosphine (54 mg, 0.206 mmol) in THF (2.5 mL) at rt was added DEAD (0.0324 mL, 0.206 mmol). After 1 min, a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one (Preparation K, 80 mg, 0.172 mmol) in THF (2.5 mL) was added. After 2 min, 2-hydroxypyridine (16.4 mg, 0.172 mmol) was added and the mixture was stirred at rt for 3.5 h. pH 7 buffer was added and the mixture was extracted with ethyl acetate. The combined organic phases were washed with sat. aqueous NaCl, dried (MgSO4), and concentrated in vacuo. Flash chromatography (silica gel, 0-100% ethyl acetate/hexane) gave 39.7 mg of the title compound as an opaque oil: 1H NMR (CDCl3, 300 MHz) δ 2.17-2.22 (1H, m), 2.32-2.42 (2H, m), 2.74 (1H, dd, J=3, 12 Hz), 3.20 (2H, m), 3.50 (1H, m), 3.78 (1H, m), 4.80 (1H, m), 4.97 (1H, s), 5.02 (1H, s), 5.38 (1H, m), 6.51 (2H, m), 6.66 (1H, m), 6.72 (1H, d, J=9 Hz), 6.81 (1H, t, J=6 Hz), 7.18-7.36 (10H, m), 7.52 (1H, m), 8.04 (1H, m). HPLC retention time: 1.52 min (method A). MS (ESI) (M+H)+ 542.15.

後処理

  1. waitAfter 2 min
  2. additionbuffer was added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe combined organic phases were washed with sat. aqueous NaCl
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-4e664902d4d3405498405d4080c495b0
出典データセット
uspto-grants-2008_06
特許番号
US07388007B2

反応ノート

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