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Trifluoroacetic acid → methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate

HRID 452014
ノート
印刷プレビュー

反応式

HRID 452014 の反応式
[NH2:1][C@@H:2]([CH2:15][C@H:16]1[CH2:21][CH2:20][CH2:19][O:18][CH2:17]1)[CH2:3][N:4]([CH3:14])[C:5](=[O:13])[O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10].CCN(C(C)C)C(C)C.C1N=CN([C:36]([N:38]2[CH:42]=N[CH:40]=[CH:39]2)=[O:37])C=1.[Cl:43][C:44]1[CH:45]=[C:46]([C@@H:50]([C@@H:59]2CCCN[CH2:60]2)[O:51][CH2:52][CH2:53][NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:47]=[CH:48][CH:49]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:43][C:44]1[CH:45]=[C:46]([C@@H:50]([C@@H:59]2[CH2:60][CH2:40][CH2:39][N:38]([C:36](=[O:37])[NH:1][C@@H:2]([CH2:15][C@H:16]3[CH2:21][CH2:20][CH2:19][O:18][CH2:17]3)[CH2:3][N:4]([C:5]([O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10])=[O:13])[CH3:14])[CH2:42]2)[O:51][CH2:52][CH2:53][NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:47]=[CH:48][CH:49]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 580174332-(trimethylsilyl)ethyl (S)-2-amino-3-((R)-tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamateHCID 59598478Carbamic acid,N-[2-[(R)-(3-chlorophenyl)(3R)-3-piperidinylmethoxy]ethyl]-,methyl ester

生成物 1

HCID 67363897
methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate
収率 75%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

At 0° C., to a solution of 2-(trimethylsilyl)ethyl (S)-2-amino-3-((R)-tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamate (1.9 g, 6 mmol) and DIPEA (3.87 g, 30 mmol) in anhydrous CH2Cl2 (20 mL) was added CDI (1.26 g, 7.8 mmol). After addition, the mixture was stirred for 1 hr at 0° C., followed by addition of methyl 2-((R)-(3-chlorophenyl)((R)-piperidin-3-yl)methoxy)ethylcarbamate as TFA salt (2.8 g, 6.6 mmol) in anhydrous CH2Cl2 (20 mL). The reaction mixture was allowed to warm to rt and stirred overnight. After the reaction was completed, the solvent was removed in vacuo. The product was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1→2:1) to afford methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate (3.0 g, 75% yield).

後処理

  1. additionAfter addition
  2. temperatureto warm to rt
  3. stirringstirred overnight
  4. customthe solvent was removed in vacuo
  5. customThe product was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1→2:1)

出典と根拠

ORDレコード
ord-f398c4f705944c6ba50f2a3fdcfa6927
出典データセット
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08487108B2

反応ノート

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