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

HRID 132942

反応式

HRID 132942 の反応式
[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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-e5deb229de0b44039d51bc1d394b7c51
出典データセット
uspto-grants-2008_06
特許番号
US07388007B2

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