2-(3-Methoxy-allylidene)-malonic acid dimethyl ester → (S)-3-[2-tert-Butoxycarbonyl-2-(3-methoxycarbonyl-2-oxo-2H-pyridin-1-yl)-ethyl]-indole-1-carboxylic acid tert-butyl ester

HRID 1809485

Reaction equation

HRID 1809485 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][C@H:18]([NH2:26])[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27][O:28][C:29](=[O:40])[C:30](=[CH:35][CH:36]=[CH:37]OC)[C:31](OC)=[O:32].C[O-].[Na+]>CO.O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][C@@H:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[N:26]2[CH:37]=[CH:36][CH:35]=[C:30]([C:29]([O:28][CH3:27])=[O:40])[C:31]2=[O:32])=[CH:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 3

HCID 5979922-(3-Methoxy-allylidene)-malonic acid dimethyl esterHCID 7021141tert-butyl 3-[(2S)-2-amino-3-(tert-butoxy)-3-oxopropyl]-1H-indole-1-carboxylateHCID 10942334Sodium Methoxide

Product 1

HCID 58674958(S)-3-[2-tert-Butoxycarbonyl-2-(3-methoxycarbonyl-2-oxo-2H-pyridin-1-yl)-ethyl]-indole-1-carboxylic acid tert-butyl esterYield 66.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of (S)-3-(2-Amino-2-tert-butoxycarbonyl-ethyl)-indole-1-carboxylic acid tert-butyl ester (2.5 g, 7 mmol) in methanol (15 ml) was added 2-(3-methoxy-allylidene)-malonic acid dimethyl ester (1.5 g, 7 mmol) and stirred overnight at room temperature. Sodium methoxide (78 mg, 1.4 mmol) was added and stirred for three hours at room temperature. The reaction mixture was diluted with water (50 ml) and extracted with ethylacetate (60 ml). The organic layer was washed with brine, dried (MgSO4), filtered and evaporated to afford the crude product, which was perified by flash chromatography (30-70% ethylacetate/petroleum ether) to afford the title compound as a white solid (2.3 g, 57%); 1H NMR (400 MHz, CDCl3) δ 1.43 (9H, s), 1.72 (9H, s), 3.50 (2H, m), 3.91 (3H, m), 5.68 (1H, br s), 6.08 (1H, t), 7.2-7.5 (5H, m), 8.15 (2H, m); M+H 497.5, M−H 495.5.

Workup

  1. stirringstirred for three hours at room temperature
  2. extractionextracted with ethylacetate (60 ml)
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto afford the crude product, which

Sources & evidence

ORD record
ord-38fcff9909d849b1905c205bec0fe92c
Source dataset
uspto-grants-2013_01
Patent number
US08362043B2

Linked notes

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