2,2-Dimethoxypropane → (3aR,4R,9bR)-benzyl 4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinoline-1-carboxylate

HRID 592108

Reaction equation

[CH3:1][O:2][CH2:3][C:4](=[C:12]1[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[C:13]1=O)[NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.N1C(=O)NC(=O)NC1=O.COC(OC)(C)C>CC(C)=O>[CH3:1][O:2][CH2:3][C@H:4]1[C@H:12]2[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[C@H:13]2[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5]1

Participants

Conditions

Temperature: 60 °C

Procedure

In a 120 mL stainless autoclave were charged benzyl 3-(2-methoxy-1-(phenylamino)ethylidene)-2-oxopyrrolidine-1-carboxylate (1.50 g) [mw. 366.41, 4.1 mmol], cyanuric acid (0.53 g) [mw. 129.07, 4.1 mmol] and RuBr2[(s,s)-ptbp-skewphos](pica) (42.4 mg) [mw. 1033.94, 0.041 mmol]synthesized in Reference Example 52, and the system was substituted with argon. To deaeration-treated dehydrated acetone (55 mL) was added 2,2-dimethoxypropane (1.5 mL) [mw. 104.15, d=0.85, 12.3 mmol, 3.0 eq.] and the mixture was added to the autoclave by argon pressure supply. Furthermore, 2,2-dimethoxypropane was rinsed with dehydrated acetone (5 mL), and added by argon pressure supply. Hydrogen was filled therein to 5 MPa, and the mixture was stirred at a reaction temperature of 60° C. for 46 hr. The reaction mixture was cooled to room temperature and depressurized. Quantification by high performance liquid chromatography confirmed that the starting material, benzyl 3-(2-methoxy-1-(phenylamino)ethylidene)-2-oxopyrrolidine-1-carboxylate, remained, the reaction intermediate, benzyl 3-(2-methoxy-1-(phenylamino)ethyl)-2-oxopyrrolidine-1-carboxylate, was not more than 1%, and the resultant product, (3aR,4R,9bR)-benzyl 4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinoline-1-carboxylate, was also not more than 1%.

Workup

customsynthesized in Reference Example 52
additionthe mixture was added to the autoclave by argon pressure supply
washFurthermore, 2,2-dimethoxypropane was rinsed with dehydrated acetone (5 mL)
additionadded by argon pressure supply
additionHydrogen was filled
temperatureThe reaction mixture was cooled to room temperature

Sources & evidence

ORD record: ord-060bc22bfcf24b07b4d1217efcda3c8d
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238667B2

Linked notes

Loading…