Acetic Acid → 5,8-dimethoxy-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H chromene-2-carboxylic acid methyl ester

HRID 1925906Notes

Reaction equation

HRID 1925906 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[C:15]([CH:16]=O)=[CH:14][C:13]2[C:8](=[C:9]([O:20][CH3:21])[CH:10]=[CH:11][C:12]=2[O:18][CH3:19])[O:7]1)=[O:5])C.[CH3:22][O:23][C:24](=[O:31])[C@@H:25]([NH2:30])[CH2:26][CH:27]([CH3:29])[CH3:28].CCN(C(C)C)C(C)C.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[CH3:1][O:3][C:4]([CH:6]1[C:15]([CH2:16][NH:30][C@H:25]([C:24]([O:23][CH3:22])=[O:31])[CH2:26][CH:27]([CH3:29])[CH3:28])=[CH:14][C:13]2[C:8](=[C:9]([O:20][CH3:21])[CH:10]=[CH:11][C:12]=2[O:18][CH3:19])[O:7]1)=[O:5]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 65105(+)-L-Leucine methyl esterHCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 866605383-formyl-5,8-dimethoxy-2H-chromene-2-carboxylic acid ethyl ester

Product 1

HCID 675213365,8-dimethoxy-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H chromene-2-carboxylic acid methyl esterYield 41.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 3-formyl-5,8-dimethoxy-2H-chromene-2-carboxylic acid ethyl ester (5.0 g, 17.11 mmol) (Example 13, Step 1) in methanol (40 mL) containing molecular sieves (0.7 g) was added commercially available (S)-2-amino-4-methyl-pentanoic acid methyl ester (3.1 g, 17.11 mmol) and N,N′-diisopropylethylamine (4.42 mL, 34.21 mmol). The mixture was stirred at 25° C. for 10 hours. At this time, sodium cyanoborohydride (2.15 g, 34.21 mmol) and acetic acid (1.95 mL, 34.21 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 5,8-dimethoxy-3-[((S)-1-methoxycarbonyl-3-methyl-butylamino)-methyl]-2H chromene-2-carboxylic acid methyl ester (2.90 g, 39.2%) 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-48a0e11c8870472d94915332919027fa
Source dataset
uspto-grants-2012_05
Patent number
US08178689B2

Reaction notes

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