Diisopropylethylamine → 3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-(oxazol-2-yl)benzoic acid

HRID 20947

反応式

HRID 20947 の反応式
C(O[C:6]([N:8]1[CH2:12][C@H:11]([OH:13])C[C@@H]1C(O)=O)=O)(C)(C)C.Br[C:18]1[CH:19]=[C:20]([CH:25]=[C:26]([C:28]([N:30]2[CH2:34][CH2:33][CH2:32][C@@H:31]2[CH2:35][O:36][CH3:37])=[O:29])[CH:27]=1)[C:21]([O:23]C)=[O:22].BrC1C=C(C=C(C(OC)=O)C=1)C(O)=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.COC[C@H]1CCCN1>ClCCl>[CH3:37][O:36][CH2:35][C@H:31]1[CH2:32][CH2:33][CH2:34][N:30]1[C:28]([C:26]1[CH:25]=[C:20]([CH:19]=[C:18]([C:6]2[O:13][CH:11]=[CH:12][N:8]=2)[CH:27]=1)[C:21]([OH:23])=[O:22])=[O:29]

参加物

8

反応物 6

HCID 81531DiisopropylethylamineHCID 671216(2R)-2-(Methoxymethyl)pyrrolidineHCID 688616N-Boc-cis-4-hydroxy-D-prolineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 225936413-Bromo-5-(methoxycarbonyl)benzoic acidHCID 67315972(R)-methyl 3-bromo-5-(2-(methoxymethyl)pyrrolidine-1-carbonyl)benzoate

生成物 1

HCID 593468493-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-(oxazol-2-yl)benzoic acid収率 73%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

Step H (1): (R)-methyl 3-bromo-5-(2-(methoxymethyl)pyrrolidine-1-carbonyl)benzoate. To a solution of 3-bromo-5-(methoxycarbonyl)benzoic acid (1.8 g, 6.95 mmol) in dichloromethane (100 mL) and was added Hunig's base (2.7 g, 20.85 mmol) to make a clear solution and HATU (3.17 g, 8.34 mmol) was then added. After stirring for 30 min, the reaction mixture was added (R)-2-(methoxymethyl)pyrrolidine (800 mg, 6.95 mmol) and the reaction mixture was stirred at rt for 6 h. Dichloromethane (100 mL) was added and the mixture was washed with 1N NaOH, H2O and concentrated under vacuum. The crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% EtOAc/Hexane step gradient) to give 1.8 g of the title compound (73% yield): 1H NMR (CDCl3, 500 MHz) δ ppm 1.77-2.08 (4H, m), 3.14-3.47 (5H, m), 3.63 (2H, brd s), 3.82 (3H, s), 4.41 (1H, brd s), 7.83 (1H, s), 8.07 (1H, s), 8.20 (1H, m).

後処理

  1. additionwas then added
  2. stirringthe reaction mixture was stirred at rt for 6 h
  3. washthe mixture was washed with 1N NaOH, H2O
  4. concentrationconcentrated under vacuum
  5. customThe crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% EtOAc/Hexane step gradient)

出典と根拠

ORDレコード
ord-0cc5c90e166c4f5b9e2b634346869be7
出典データセット
uspto-grants-2010_06
特許番号
US07745470B2

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