Diisopropylethylamine → (2S,5S)-1-tert-butyl 2-(3-chloro-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-9-yl) 5-methylpyrrolidine-1,2-dicarboxylate

HRID 1751745Notes

Reaction equation

HRID 1751745 reaction equation
Br[CH:2]1[CH2:20][CH2:19][C:5]2=[CH:6][C:7]3[C:8]4[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:9]=4[CH2:10][O:11][C:12]=3[CH:13]=[C:4]2[C:3]1=[O:21].[C:22]([O:26][C:27]([N:29]1[C@@H:33]([CH3:34])[CH2:32][CH2:31][C@H:30]1[C:35]([OH:37])=[O:36])=[O:28])([CH3:25])([CH3:24])[CH3:23].CCN(C(C)C)C(C)C>CC#N.CCOC(C)=O>[CH3:34][C@@H:33]1[N:29]([C:27]([O:26][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:28])[C@H:30]([C:35]([O:37][CH:2]2[CH2:20][CH2:19][C:5]3=[CH:6][C:7]4[C:8]5[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:9]=5[CH2:10][O:11][C:12]=4[CH:13]=[C:4]3[C:3]2=[O:21])=[O:36])[CH2:31][CH2:32]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 15516206(5S)-1-(tert-Butoxycarbonyl)-5-methyl-L-prolineHCID 696732929-bromo-3-chloro-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one

Product 1

HCID 69675575(2S,5S)-1-tert-butyl 2-(3-chloro-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-9-yl) 5-methylpyrrolidine-1,2-dicarboxylateYield 82.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 9-bromo-3-chloro-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (1.41 g, 3.88 mmol) in MeCN (17 mL) was added (2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid (980 mg, 4.27 mmol) and DIPEA (1.49 mL, 8.54 mmol). After stirring for 18 h at 50° C., the solution was diluted with EtOAc and washed successively with 1N HCl, saturated aqueous NaHCO3 and brine. The organics were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (10% to 30% EtOAc/hexanes) to afford (2S,5S)-1-tert-butyl 2-(3-chloro-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-9-yl) 5-methylpyrrolidine-1,2-dicarboxylate (1.63 g, 81%).

Workup

  1. washwashed successively with 1N HCl, saturated aqueous NaHCO3 and brine
  2. dry with materialThe organics were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue was purified by silica column chromatography (10% to 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-02d6751eae2848e292698e1bafbc64f6
Source dataset
uspto-grants-2015_10
Patent number
US09156823B2

Reaction notes

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