ChemicalBook CAS DataBase List (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-cyano-2,6-dimethylphenyl)propanoate

(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-cyano-2,6-dimethylphenyl)propanoate synthesis

5synthesis methods

Product Name:(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-cyano-2,6-dimethylphenyl)propanoate
CAS Number:1227311-10-5
Molecular formula:C18H24N2O4
Molecular Weight:332.39

75344-77-3 Synthesis

75344-77-3
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93267-04-0 Synthesis

93267-04-0
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(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-cyano-2,6-dimethylphenyl)propanoate

1227311-10-5
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Yield:1227311-10-5 50%

Reaction Conditions:

Stage #1: N-(tert-butoxycarbonyl)-L-3-iodoalanine methyl esterwith iodine;zinc in N,N-dimethyl-formamide at 20; for 0.666667 h;Inert atmosphere;
Stage #2: 4-bromo-3,5-dimethyl benzonitrilewith dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane;tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ in N,N-dimethyl-formamide at 50;Temperature;

Steps:

A5.1; B8.1 Step 1: Synthesis of methyl OSy2-(Yfer/-butoxycarbonvOamino)-3-(4-cvano- 2.6-dim ethyl phenyl ipropanoate

To a stirred suspension of zinc powder (2.1 g, 32.3 mmol) in anhydrous N,N-d m ethyl form a ide (10 mL) under nitrogen was added iodine (170 mg). After 5min, a solution of methyl (i?)-2-((/er/-butoxycarbonyl)amino)-3-iodopropanoate (4.2 g, 12.8 mmol) in A( A'-di m ethyl form a i de (10 mL) was added slowly over lOmin. The mixture was stirred at rt for 30min. A suspension of 4-bromo-3,5-dimethylbenzonitrile (2.5 g, 12 mmol), Pd₂(dba)₃ (205 mg, 0.22 mmol), and 2-dicyclohexylphosphino-2',6'- dimethoxybiphenyl (Sphos, 210 mg, 0.51 mmol) in A( A-di m eth yl form am i de (10 mL) was added into the zinc reagent mixture. The reaction mixture was heated at 50°C and stirred overnight. After cooling, the reaction mixture was quenched with water, diluted with EtOAc and filtered through Celite. The filter cake was washed with EtOAc and the filtrate was washed with brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography over silica gel (0-20% EtOAc/CH₂Cl₂) to afford the desired product as a white solid (2.0 g, 50%). LC-MS: 355.2 [M+Na]⁺; 1H NMR (400MHz, CDCl₃) d 7.30 (s, 2H), 5.13 (d, 1H, J = 8.8 Hz), 4.56 (q, 1H, J = 8.0 Hz), 3.67 (s, 3H), 3.15-3.00 (m, 2H), 2.38 (s, 6H), 1.35 (s, 9H).

References:

WO2019/195634,2019,A1 Location in patent:Page/Page column 87-88; 151-152

4326-36-7 Synthesis