Diisopropylethylamine → (2S,4S)-1-tert-butyl 2-(3-chloro-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-9-yl) 4-ethoxypyrrolidine-1,2-dicarboxylate

HRID 2172476Notes

Reaction equation

HRID 2172476 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[CH2:33][C@@H:32]([O:34][CH2:35][CH3:36])[CH2:31][C@H:30]1[C:37]([OH:39])=[O:38])=[O:28])([CH3:25])([CH3:24])[CH3:23].CCN(C(C)C)C(C)C>CC#N.CCOC(C)=O>[CH2:35]([O:34][C@@H:32]1[CH2:33][N:29]([C:27]([O:26][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:28])[C@H:30]([C:37]([O:39][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:38])[CH2:31]1)[CH3:36]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 15222300(2S,4S)-1-(tert-butoxycarbonyl)-4-ethoxypyrrolidine-2-carboxylic acidHCID 696732929-bromo-3-chloro-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one

Product 1

HCID 69675491(2S,4S)-1-tert-butyl 2-(3-chloro-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-9-yl) 4-ethoxypyrrolidine-1,2-dicarboxylateYield 56.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a slurry of 9-bromo-3-chloro-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (2.50 g, 6.8 mmol) in MeCN (20 mL) was added (2S,4S)-1-(tert-butoxycarbonyl)-4-ethoxypyrrolidine-2-carboxylic acid (2.68 g, 10.3 mmol) and DIPEA (1.3 mL, 7.5 mmol). The reaction was heated with stirring to 50° C. for 18 h. The reaction was then cooled to room temperature and diluted with EtOAc. The solution was washed with HCl (1N) and brine. The aqueous layers were backextracted with EtOAc and the resulting organic layers were combined, dried (Na2SO4) and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (15% to 50% EtOAc/Hexanes) to afford (2S,4S)-1-tert-butyl 2-(3-chloro-8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-9-yl) 4-ethoxypyrrolidine-1,2-dicarboxylate (2.08 g, 56%).

Workup

  1. temperatureThe reaction was heated
  2. temperatureThe reaction was then cooled to room temperature
  3. washThe solution was washed with HCl (1N) and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified by silica column chromatography (15% to 50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-f07fcccd2a054d4aae3a8683f0655750
Source dataset
uspto-grants-2015_06
Patent number
US09051340B2

Reaction notes

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