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

HRID 1925898Notes

Reaction equation

HRID 1925898 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:29])[C@@H:23]([NH2:28])[CH2:24][CH:25]([CH3:27])[CH3:26].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:28][C@H:23]([C:22]([O:21][CH3:20])=[O:29])[CH2:24][CH:25]([CH3:27])[CH3:26])=[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 65105(+)-L-Leucine methyl esterHCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 866605375-methoxy-3-formyl-2H-chromene-2-carboxylic acid ethyl ester

Product 1

HCID 675204455-methoxy-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl esterYield 43.3%

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 (Example 7, step 1) (1.0 g, 3.81 mmol) in methanol (20 mL) containing molecular sieves (0.7 g) was added commercially available (S)-2-amino-4-methyl-pentanoic acid methyl ester (0.77 g, 6.86 mmol) and N,N′-diisopropylethylamine (0.99 mL, 7.63 mmol). The mixture was stirred at 25° C. for 10 hours. At this time, sodium cyanoborohydride (0.48 g, 7.63 mmol) and acetic acid (0.8 mL, 13.72 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 1:9, Rf=0.45) over neutral alumina afforded 5-methoxy-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester (0.45 g, 43.3%) 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-691523f304ef4fe3ab455fb125707058
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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