Acetic Acid → 5-methoxy-3-[((S)-2-cyclohexyl-1-methoxycarbonyl-ethylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester

HRID 1925891Notes

Reaction equation

HRID 1925891 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[C:15]([CH:16]=O)=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[O:18][CH3:19])[O:7]1)=[O:5])[CH3:2].[CH3:20][O:21][C:22](=[O:32])[C@@H:23]([NH2:31])[CH2:24][CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.CCN(C(C)C)C(C)C.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[CH2:1]([O:3][C:4]([CH:6]1[C:15]([CH2:16][NH:31][C@H:23]([C:22]([O:21][CH3:20])=[O:32])[CH2:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[O:18][CH3:19])[O:7]1)=[O:5])[CH3:2]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 13833920Methyl 3-cyclohexyl-L-alaninateHCID 866605375-methoxy-3-formyl-2H-chromene-2-carboxylic acid ethyl ester

Product 1

HCID 675216525-methoxy-3-[((S)-2-cyclohexyl-1-methoxycarbonyl-ethylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl esterYield 46.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 5-methoxy-3-formyl-2H-chromene-2-carboxylic acid ethyl ester (1.3 g, 4.96 mmol) in methanol (20 mL) containing molecular sieves (0.7 g) was added commercially available (S)-2-amino-3-cyclohexyl-propionic acid methyl ester (1.2 g, 5.45 mmol) and N,N′-diisopropylethylamine (1.71 mL, 9.91 mmol). The mixture was stirred at 25° C. for 10 hours. At this time, sodium cyanoborohydride (0.62 g, 9.91 mmol) and acetic acid (0.47 mL, 7.49 mmol) were added simultaneously to the reaction mixture, and the reaction mixture was stirred for additional 16 hours at 25° C. The reaction mixture was then filtered through celite and washed with methanol. The filtrate was concentrated in vacuo. Flash column chromatography (eluant-ethyl acetate:petroleum ether 1:19, Rf=0.6) over neutral alumina afforded 5-methoxy-3-[((S)-2-cyclohexyl-1-methoxycarbonyl-ethylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester (1.0 g, 45.5%) as an oil.

Workup

  1. stirringthe reaction mixture was stirred for additional 16 hours at 25° C
  2. filtrationThe reaction mixture was then filtered through celite
  3. washwashed with methanol
  4. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-585f54d988174435b75726996da275ef
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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