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

HRID 132942

반응식

HRID 132942 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.OCC1COCCN1C(OC(C)(C)C)=O.C(OC(N1CCOCC1C(O)=O)=O)(C)(C)C.CCN(C(C)C)C(C)C.ClCCOC=O.[BH4-].[Na+]>C1COCC1.CO>[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 81531DiisopropylethylamineHCID 2467482-Chloroethyl formateHCID 27601334-(tert-Butoxycarbonyl)morpholine-3-carboxylic acidHCID 4311764Sodium borohydrideHCID 5058359Tert-butyl 3-(hydroxymethyl)morpholine-4-carboxylateHCID 67316078(4S,5S)-4-(3,5-difluorobenzyl)-5-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)oxazolidin-2-one

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 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

Step L (1): tert-Butyl 3-(hydroxymethyl)morpholine-4-carboxylate. To a solution of 4-(tert-butoxycarbonyl)morpholine-3-carboxylic acid (4.7 g, 20.35 mmol) in THF (120 mL) were added Hunig's base (6.6 g, 50.875 mmol). Then chloroethylformate (2.65 g, 24.4 mmol) was added at 0° C. After stirring from 0° C. to rt over 1.5 h, NaBH4 (3.1 g, 81.4 mmol) was added and after 15 min, MeOH (20 mL) was added slowly at 0° C. After stirring at rt for 1 h, THF and MeOH was removed and ethyl acetate (600 mL) was added and the mixture was washed with NaHCO3, H2O, and dried (Na2SO4), and concentrated in vacuo. 3.56 g of product was obtained as the title compound (81% yield): 1H NMR (CDCl3, 500 MHz) δ 1.46 (9H, s), 2.03 (1H, brd s), 3.17 (1H, m), 3.46 (1H, m), 3.56 (1H, m), 3.72-3.86 (4H, m), 3.91 (1H, d, J=10 Hz), 3.99 (1H, brd s).

후처리

  1. stirringAfter stirring at rt for 1 h
  2. customTHF and MeOH was removed
  3. additionethyl acetate (600 mL) was added
  4. washthe mixture was washed with NaHCO3, H2O
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-e5deb229de0b44039d51bc1d394b7c51
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07388007B2

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