Diisopropylethylamine → HCID 89675352, compound

HRID 1509665Notes

Reaction equation

HRID 1509665 reaction equation
Br[CH:2]1[C:20](=[O:21])[C:6]2=[CH:7][CH:8]=[C:9]3[C:14]([O:13][CH2:12][C:11]4[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:10]3=4)=[C:5]2[CH2:4][CH2:3]1.[N:22]1([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:29][CH2:28][CH2:27][C@H:23]1[C:24]([OH:26])=[O:25].C(N(C(C)C)CC)(C)C>C(#N)C.C(OCC)(=O)C>[N:22]1([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:29][CH2:28][CH2:27][CH:23]1[C:24]([O:26][C@@H:2]1[C:20](=[O:21])[C:6]2=[CH:7][CH:8]=[C:9]3[C:14]([O:13][CH2:12][C:11]4[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:10]3=4)=[C:5]2[CH2:4][CH2:3]1)=[O:25]

Participants

6

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-2×HCID 89590763HCID 89590763, compound

Product 1

HCID 89675352HCID 89675352, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-bromo-8-chloro-2,3,4,6-tetrahydro-1H-dibenzo[c,h]chromen-1-one (1.05 g, 2.9 mmol) and Boc-Pro-OH (1.75 g, 8.1 mmol) in acetonitrile (9.0 mL) was added diisopropylethylamine (1.5 mL, 8.7 mmol). The solution was stirred under argon at 50° C. for two hours. Extra Boc-Pro-OH (620 mg, 2.9 mmol) and diisopropylethylamine (0.5 mL, 2.9 mmol) were added and the reaction was stirred at 50° C. for 16 hours. The reaction was cooled to room temperature and diluted with ethyl acetate. The organics were washed with water and brine, dried with magnesium sulfate and concentrated. The crude material was purified by flash column chromatography and the product (2S)-1-tert-butyl 2-(8-chloro-1-oxo-2,3,4,6-tetrahydro-1H-dibenzo[c,h]chromen-2-yl) pyrrolidine-1,2-dicarboxylate was isolated as a mixture of diastereomers (0.99 g, 69% yield).

Workup

  1. stirringthe reaction was stirred at 50° C. for 16 hours
  2. temperatureThe reaction was cooled to room temperature
  3. washThe organics were washed with water and brine
  4. dry with materialdried with magnesium sulfate
  5. concentrationconcentrated
  6. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-a274b290d6024a1db9a43236df43ece5
Source dataset
uspto-grants-2015_12
Patent number
US09221833B2

Reaction notes

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