HRID1158381

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID8471

Triethylamine

C6H15N

HCID152842

Bis(2-oxo-3-oxazolidinyl)phosphinic chloride

C6H8ClN2O5P

HCID59512399

未命名化合物

结构：CC(C)NC[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]1C(C)(C)O[SiH2]C(C)(C)C

HCID131728361

未命名化合物

PRODUCTS

生成物

结构：COCCCn1cc(C)c2ccc(C(=O)N(C[C@@H]3CN(C(=O)OC(C)(C)C)C[C@H]3C(C)(C)O[SiH2]C(C)(C)C)C(C)C)cc21

HCID178495140

未命名化合物

AUXILIARIES

试剂、催化剂与溶剂

溶剂HCID6344

Dichloromethane

CH2Cl2

PROCEDURE

实验过程

A mixture of (3S,4R)-3-(tert-butyl-dimethyl-silanyloxymethyl)-4-(isopropylamino-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (8.5 g, 22 mmol), 1-(3-methoxy-propyl)-3-methyl-1H-indole-6-carboxylic acid (7.6 g, 30.8 mmol), bis(2-oxo-3-oxazolidinyl)phosphinic chloride (7.84 g, 30.8 mmol) and triethylamine (12.3 mL, 88 mmol) in CH2Cl2 (425 mL) is refluxed overnight under a nitrogen atmosphere and then quenched by the addition of an aqueous saturated solution of NaHCO3. The organic layer is separated, and the aqueous phase is extracted 3 times with AcOEt. The combined organic extracts are concentrated in vacuo. The residual oil is taken up in a mixture of THF and MeOH, NaOH 1N is added to cleave the anhydride side product and the mixture stirred for 3 h. The solvents are concentrated, CH2Cl2 is added and the layers are separated. The aqueous one is then back extracted twice with CH2Cl2 and the combined organic extracts are washed with brine, dried over Na2SO4, filtered and concentrated. The crude product is used in the next step without further purification. TLC, Rf (AcOEt)=0.6. MS (LC-MS): 516.3 [M-Boc+H]+; tR (HPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN an H2O containing 0.1% TFA, flow: 1.5 mL/min): 8.60 min.

WORKUP

后处理

temperatureis refluxed overnight under a nitrogen atmosphere
customquenched by the addition of an aqueous saturated solution of NaHCO3
customThe organic layer is separated
extractionthe aqueous phase is extracted 3 times with AcOEt
concentrationThe combined organic extracts are concentrated in vacuo
additionThe residual oil is taken up in a mixture of THF and MeOH, NaOH 1N
additionis added
concentrationThe solvents are concentrated
additionCH2Cl2 is added
customthe layers are separated
extractionThe aqueous one is then back extracted twice with CH2Cl2
washthe combined organic extracts are washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude product is used in the next step without further purification
customHPLC, Macherey-Nagel Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN
custom8.60 min.

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-ab8328b0cffa4b6a80ab0cd4c6269a79
来源数据集: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
专利: US07807709B2
来源说明: uspto-grants-2010_10

反应 SMILES

[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][CH:15]([CH3:17])[CH3:16])[C@H:10]([C:18]([CH3:26])([CH3:25])[O:19][SiH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27][O:28][CH2:29][CH2:30][CH2:31][N:32]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([C:41](O)=[O:42])[CH:39]=2)[C:34]([CH3:44])=[CH:33]1.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(CC)CC)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:15]([CH3:16])[CH3:17])[C:41]([C:38]2[CH:39]=[C:40]3[C:35]([C:34]([CH3:44])=[CH:33][N:32]3[CH2:31][CH2:30][CH2:29][O:28][CH3:27])=[CH:36][CH:37]=2)=[O:42])[C@H:10]([C:18]([CH3:26])([CH3:25])[O:19][SiH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]