Diisopropylethylamine → trans-3-(3-Cyano-phenylcarbamoyl)-4-(3-methoxycarbonyl-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1524289Notes

Reaction equation

HRID 1524289 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13](=[O:23])[NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]#[N:22])[CH:16]=2)[C@H:10]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[OH:32].C1[CH2:37][O:36][CH2:35]C1.C(N(CC)C(C)C)(C)C>CCOC(C)=O.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@@H:10]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:35]([O:36][CH3:37])=[O:32])[CH:25]=2)[C@H:11]([C:13](=[O:23])[NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]#[N:22])[CH:16]=2)[CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 21899815MeOH tetrahydrofuranHCID 68089325trans-3-(3-Bromo-phenyl)-4-(3-cyano-phenylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68089439trans-3-(3-Cyano-phenylcarbamoyl)-4-(3-methoxycarbonyl-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

Split a solution of trans-3-(3-bromo-phenyl)-4-(3-cyano-phenylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.53 g, 1.13 mmol) in a 1:1 mixture of MeOH/THF (10 mL) into three microwave pressure tubes. Add to each tube molybedinum hexacarbonyl (0.06 g, 0.23 mmol) followed by N,N-diisoproylethyl amine (0.15 mL, 0.80 mmol) and Herrmann's palladacycle (0.16 g, 0.17 mmol). Heat each mixture in a microwave reactor at 150° C. for 15 minutes then cool to room temperature. Combine the mixtures, dilute with EtOAc and load onto silica gel. Purify the residue by flash silica gel chromatography to provide 0.20 g of trans-3-(3-cyano-phenylcarbamoyl)-4-(3-methoxycarbonyl-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a foam.

Workup

  1. additionAdd to each tube molybedinum hexacarbonyl (0.06 g, 0.23 mmol)
  2. temperaturethen cool to room temperature
  3. customPurify the residue by flash silica gel chromatography

Sources & evidence

ORD record
ord-9668f91fa5b74e859c7558475d5102ff
Source dataset
uspto-grants-2015_07
Patent number
US09079880B2

Reaction notes

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