Acetic Acid → (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one

HRID 132941노트

반응식

HRID 132941 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH:34]=[C:35]([F:37])[CH:36]=1)[CH2:5][C@H:6]1[C@@H:10]([C@H:11]2[CH2:15][C@@H:14]([O:16]CC=C)[CH2:13][N:12]2[CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:9][C:8](=[O:33])[NH:7]1.C(O[C@H]1C[C@H]([C@H]2OC(=O)N[C@H]2CC2C=C(F)C=C(F)C=2)N(C(C2C=CC=CC=2)C2C=CC=CC=2)C1)(=O)C.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.C(O)(=O)C>C1COCC1.C(OCC)(=O)C.CCCCCC>[F:37][C:35]1[CH:34]=[C:4]([CH:3]=[C:2]([F:1])[CH:36]=1)[CH2:5][C@H:6]1[C@@H:10]([C@H:11]2[CH2:15][C@H:14]([OH:16])[CH2:13][N:12]2[CH:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:9][C:8](=[O:33])[NH:7]1

참가 물질

9

반응물 6

HCID 176Acetic AcidHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 58608196(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-oneHCID 67316078(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)oxazolidin-2-oneHCID 69195358(3S,5R)-5-((4S,5S)-4-(3,5-difluorobenzyl)-2-oxooxazolidin-5-yl)-1-benzhydrylpyrrolidin-3-yl acetate

생성물 1

HCID 58608198(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one수율 81%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 21226206Ethyl acetate hexane용매

반응 조건

온도
0 °C

실험 절차

Step K (1): (3S,5R)-5-((4S,5S)-4-(3,5-difluorobenzyl)-2-oxooxazolidin-5-yl)-1-benzhydrylpyrrolidin-3-yl acetate. To a solution of triphenylphosphine (510 mg, 1.94 mmol) in THF (20 mL) at 0° C. was added DEAD (0.36 mL, 1.94 mmol) and the mixture was allowed to come to rt for 5 min and was again cooled to 0° C. A solution of (4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)oxazolidin-2-one (Preparation J, 750 mg, 1.62 mmol) in THF (20 mL) was added and the mixture was allowed to come to rt for 5 min and was again cooled to 0° C. Acetic acid (0.093 mL, 1.62 mmol) was added and the mixture was warmed to rt and stirred for 30 min. 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, 5-100% ethyl acetate/hexane) gave 661 mg (81% yield) of the title compound as a clear, very slightly yellow oil: 1H NMR (CDCl3, 500 MHz) δ 1.31-1.34 (1H, m), 2.08-2.16 (1H, m), 2.39 (3H, m), 2.80 (1H, brd s), 3.26 (1H, brd s), 3.60 (2H, brd s), 4.11 (1H, m), 4.27-4.33 (1H, m), 4.91 (2H, m), 5.28 (1H, m), 6.40 (2H, brd s), 6.51 (2H, m), 6.69 (1H, m), 7.22 (1H, m), 7.28-7.49 (8H, m). HPLC retention time: 1.50 min (method A). MS (ESI) (M+H)+ 507.17.

후처리

  1. waitto come to rt for 5 min
  2. temperaturewas again cooled to 0° C
  3. temperaturethe mixture was warmed to rt
  4. additionbuffer was added
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe combined organic phases were washed with sat. aqueous NaCl
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-51d3ae56f3b642b2b25b14ab78aabaf6
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07388007B2

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