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,4S)-4-(pyridin-2-yloxy)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide

HRID 132953ノート

反応式

HRID 132953 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(OCC)(=O)C.CCCCCC>[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

9

反応物 6

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 58608196(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-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 69196422(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)oxazolidin-2-oneHCID 178516071HCID 178516071、化合物

生成物 1

HCID 69196428(S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4S)-4-(pyridin-2-yloxy)pyrrolidin-2-yl)propan-2-yl)-4-phenylbutanamide収率 52%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 21226206Ethyl acetate hexane溶媒

実験手順

Step 10 (A): (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-(pyridin-2-yloxy)pyrrolidin-2-yl)oxazolidin-2-one. To a solution of triphenylphosphine (58 mg, 0.22 mmol) in THF (2.5 mL) at rt was added DEAD (0.035 mL, 0.22 mmol). After 1 min, a solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one (Preparation J, 85 mg, 0.183 mmol) in THF (2.5 mL) was added. After 2 min, 2-hydroxypyridine (17.4 mg, 0.183 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 50.7 mg (52% yield) of the title compound: 1H NMR (CDCl3, 300 MHz) δ 2.22 (1H, m), 2.38-2.55 (3H, m), 2.87 (1H, d, J=12 Hz), 3.32 (1H, dd, J=6, 12 Hz), 3.56-3.63 (2H, m), 4.70 (1H, d, J=9 Hz), 4.96 (1H, s), 5.42 (1H, s), 5.51 (1H, s), 6.47-6.53 (2H, m), 6.62-6.73 (3H, m), 6.81 (1H, t, J=6 Hz), 7.13-7.28 (5H, m), 7.37-7.42 (4H, m), 7.54 (1H, m), 8.08 (1H, m). HPLC retention time: 1.73 min (method C). MS (ESI) (M+H)+ 542.31.

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-b417036df3a8430283e56f2424270e00
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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