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Hydrochloric Acid → (S)-4-((3S,4S)-3-fluoro-1-((R)-1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)phenyl 2-amino-3-methylbutanoate hydrochloride

HRID 716091
ノート
印刷プレビュー

反応式

HRID 716091 の反応式
C(OC([NH:8][C@@H:9]([CH:40]([CH3:42])[CH3:41])[C:10]([O:12][C:13]1[CH:18]=[CH:17][C:16]([C@@H:19]2[CH2:24][CH2:23][N:22]([C@@H:25]3[CH2:29][CH2:28][N:27]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=4)[C:26]3=[O:38])[CH2:21][C@H:20]2[F:39])=[CH:15][CH:14]=1)=[O:11])=O)(C)(C)C.[ClH:43].C(OCC)C>C(Cl)Cl>[ClH:43].[NH2:8][C@@H:9]([CH:40]([CH3:42])[CH3:41])[C:10]([O:12][C:13]1[CH:18]=[CH:17][C:16]([C@@H:19]2[CH2:24][CH2:23][N:22]([C@@H:25]3[CH2:29][CH2:28][N:27]([CH2:30][C:31]4[CH:32]=[CH:33][C:34]([CH3:37])=[CH:35][CH:36]=4)[C:26]3=[O:38])[CH2:21][C@H:20]2[F:39])=[CH:15][CH:14]=1)=[O:11]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 118207672(5)-4-((3S,4S)-3-fluoro-1-((R)-1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)phenyl 2-((tert-butoxycarbonyl)amino)-3-methylbutanoate

生成物 1

HCID 118207667(S)-4-((3S,4S)-3-fluoro-1-((R)-1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)phenyl 2-amino-3-methylbutanoate hydrochloride収率 44%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of (S)-4-((3S,4S)-3-fluoro-1-((R)-1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)phenyl 2-((tert-butoxycarbonyl)amino)-3-methylbutanoate (0.025 g, 0.043 mmol) in DCM (1.5 mL) at −20° C. was added HCl in diethyl ether (2.5 ml, 2.50 mmol, 1.0 M). The reaction mixture was slowly warmed to rt over 10 min and then allowed to stir at rt for 19 h. The solvent was then removed in vacuo to provide a pale yellow semisolid. The crude product was then purified by RP-HPLC on a Sunfire C18 (250×20 mm) 5 μm column using a gradient of 10% solvent B to 75% solvent B over 12 minutes at 15 mL/min where solvent A=0.05% HCl in water and solvent B=acetonitrile. Active fractions were concentrated by lyophilization to provide 10.2 mg (44%) of (S)-4-((3S,4S)-3-fluoro-1-((R)-1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-4-yl)phenyl 2-amino-3-methylbutanoate hydrochloride, the titled compound of example 2 as an off-white solid. LC-MS (Method A) RT=2.20 min, (M+H)+=482.2. 1H NMR: (400 MHz, DMSO-d6) δ ppm 8.64-8.78 (m, 3H) 7.38-7.46 (m, 2H) 7.23 (d, J=8.53 Hz, 2H) 7.18 (s, 4H) 5.04-5.26 (m, 1H) 4.42 (d, J=9.54 Hz, 3H) 4.17-4.23 (m, 2H) 3.29-3.40 (m, 4H) 3.19-3.28 (m, 2H) 2.30 (s, 6H) 2.04-2.19 (m, 2H) 1.11 (dd, J=12.55, 7.03 Hz, 6H). 19F NMR (376 MHz, DMSO-d6) δ −183.904.

後処理

  1. customThe solvent was then removed in vacuo
  2. customto provide a pale yellow semisolid
  3. customThe crude product was then purified by RP-HPLC on a Sunfire C18 (250×20 mm) 5 μm column
  4. customover 12 minutes
  5. concentrationActive fractions were concentrated by lyophilization

出典と根拠

ORDレコード
ord-12d48679f37d4359b68b9a4c9349b168
出典データセット
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09187506B2

反応ノート

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