Triethylamine → (9S,13S)-15-benzyl 13,9-di-tert-butyl 3,11-dioxo-1-phenyl-2-oxa-4,10,12-triazapentadecane-9,13,15-tricarboxylate

HRID 56321ノート

反応式

HRID 56321 の反応式
[NH2:1][C@H:2]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3][CH2:4][C:5](=[O:14])[O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Cl.Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl.C(N(CC)CC)C.[NH2:42][C@H:43]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:44][CH2:45][CH2:46][CH2:47][NH:48][C:49]([O:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)=[O:50]>ClCCCl>[O:50]=[C:49]([NH:48][CH2:47][CH2:46][CH2:45][CH2:44][C@@H:43]([C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[NH:42][C:24](=[O:26])[NH:1][C@H:2]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3][CH2:4][C:5]([O:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:14])[O:51][CH2:52][C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 1581102N6-[(Phenylmethoxy)carbonyl]-L-lysine 1,1-dimethylethyl esterHCID 56777356L-Glutamic acid alpha-t-butyl-delta-benzyl ester hydrochloride

生成物 1

HCID 59404356(9S,13S)-15-benzyl 13,9-di-tert-butyl 3,11-dioxo-1-phenyl-2-oxa-4,10,12-triazapentadecane-9,13,15-tricarboxylate収率 229.5%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒2 回

反応条件

温度
-78 °C

実験手順

To a solution of L-Glu(OBn)-OtBu hydrochloride (3.13 mg, 9.49 mmol) and triphosgene (923 mg, 3.13 mmol) in DCE (70 mL) cooled to −78° C. was added triethylamine (2.80 mL) under nitrogen. After stirring at −78° C. for 2 h, a solution of L-Lys(Z)-OtBu (3.88 g, 10.40 mmol) and TEA (1.5 mL) in DCE (10 mL) was added. The mixture was allowed to come to room temperature over a period of 1 h and stirred at room temperature overnight. The reaction was quenched with 1N HCl, and extracted with DCM. The organic layer was dried and concentrated under reduced pressure and the residue was purified utilizing a Biotage SP4 to afford (9S,13S)-15-benzyl 13,9-di-tert-butyl 3,11-dioxo-1-phenyl-2-oxa-4,10,12-triazapentadecane-9,13,15-tricarboxylate as a colorless oil (4.71 g, 76%). 1H NMR (400 MHz, CDCl3) δ 7.34-7.29 (m, 10H), 5.13-5.04 (m, 6H), 4.97 (brs, 1H), 4.38-4.28 (m, 2H), 3.18-3.14 (m, 2H), 2.50-2.35 (m, 2H), 2.19-2.10 (m, 1H), 1.94-1.85 (m, 1H), 1.79-1.72 (m, 1H), 1.58-1.33 (m, 21H).

後処理

  1. waitto come to room temperature over a period of 1 h
  2. stirringstirred at room temperature overnight
  3. customThe reaction was quenched with 1N HCl
  4. extractionextracted with DCM
  5. customThe organic layer was dried
  6. concentrationconcentrated under reduced pressure
  7. customthe residue was purified

出典と根拠

ORDレコード
ord-584c11a67bda4fa8ad7657a9801cdeec
出典データセット
uspto-grants-2016_09
特許番号
US09433594B2

反応ノート

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