Diisopropylethylamine → (2S,5S)-2-oxo-2-(8-oxo-8,9,10,11-tetrahydro-5H-dibenzo [c,g]chromen-3-yl)ethyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylate

HRID 1431827Notes

Reaction equation

HRID 1431827 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]2[C:17]3[CH:16]=[C:15]4[CH2:18][CH2:19][CH2:20][C:21](=[O:22])[C:14]4=[CH:13][C:12]=3[O:11][CH2:10][C:9]=2[CH:23]=1)=[O:4].[CH3:24][O:25][C:26]([NH:28][C@@H:29]([CH:41]([CH3:43])[CH3:42])[C:30]([N:32]1[C@@H:36]([CH3:37])[CH2:35][CH2:34][C@H:33]1[C:38]([OH:40])=[O:39])=[O:31])=[O:27].CCN(C(C)C)C(C)C>CC#N.CCOC(C)=O>[CH3:24][O:25][C:26]([NH:28][C@@H:29]([CH:41]([CH3:43])[CH3:42])[C:30]([N:32]1[C@@H:36]([CH3:37])[CH2:35][CH2:34][C@H:33]1[C:38]([O:40][CH2:2][C:3](=[O:4])[C:5]1[CH:6]=[CH:7][C:8]2[C:17]3[CH:16]=[C:15]4[CH2:18][CH2:19][CH2:20][C:21](=[O:22])[C:14]4=[CH:13][C:12]=3[O:11][CH2:10][C:9]=2[CH:23]=1)=[O:39])=[O:31])=[O:27]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 67412687L-Proline, N-(methoxycarbonyl)-L-valyl-5-methyl-, (5S)-HCID 866883423-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one

Product 1

HCID 69672293(2S,5S)-2-oxo-2-(8-oxo-8,9,10,11-tetrahydro-5H-dibenzo [c,g]chromen-3-yl)ethyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylateYield 99.6%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (750 mg, 2.02 mmol) in MeCN (20 mL) was added (2S,5S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylic acid (600 mg, 2.09 mmol) and DIPEA (0.35 mL, 2.02 mmol) and the solution was heated to 60° C. After stirring for 4 h, the solution was cooled to rt, and diluted with EtOAc and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (40% to 80% EtOAc/hexanes) to afford (2S,5S)-2-oxo-2-(8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)ethyl 1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-5-methylpyrrolidine-2-carboxylate (1.16 g, quant.).

Workup

  1. temperaturethe solution was cooled to rt
  2. washwashed successively with saturated aqueous NaHCO3 and brine
  3. dry with materialThe organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified by silica column chromatography (40% to 80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-8b4b3ad326464600a53f1a199c6c8792
Source dataset
uspto-grants-2015_01
Patent number
US08940718B2

Reaction notes

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