Tributylamine → tert-butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy)phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate

HRID 2054749

Reaction equation

HRID 2054749 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([CH:8]2[CH:12]=[CH:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9]2)[CH:7]=1.[C:21]([Si:25]([O:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31](I)[CH:30]=1)([CH3:27])[CH3:26])([CH3:24])([CH3:23])[CH3:22].C(N(CCCC)CCCC)CCC.C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Si:25]([O:28][C:29]1[CH:34]=[C:33]([CH:11]2[CH:12]=[C:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[F:20])[CH2:9][N:10]2[C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH:32]=[CH:31][CH:30]=1)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:27])[CH3:26]

Participants

7

Reactant 4

HCID 7622TributylamineHCID 11773TriphenylarsineHCID 27572803-(t-Butyldimethylsiloxy)iodobenzeneHCID 59656601tert-butyl 3-(5-chloro-2-fluorophenyl)-2,3-dihydro-1H-pyrrole-1-carboxylate

Product 1

HCID 59682334tert-butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy)phenyl)-4-(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A deoxygenated mixture of tert-butyl 3-(5-chloro-2-fluorophenyl)-2,3dihydro-1H-pyrrole-1-carboxylate (3-1, 1.100 g, 3.69 mmol, 1 equiv), tert-butyl(3-iodophenoxy)dimethylsilane (1.85 g, 5.54 mmol, 1.50 equiv), tributylamine (1.76 mL, 7.39 mmol, 2.00 equiv), triphenylarsine (0.453 g, 1.48 mmol, 0.400 equiv), and palladium acetate (0.166 g, 0.739 mmol, 0.200 equiv) in DMF (10 mL) was heated at 65° C. for 20 h. The reaction mixture was partitioned between water (100 mL) and ethyl acetate (2×85 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (100% hexanes initially, grading to 50% ethyl acetate in hexanes) to provide tert-butyl 2-(3-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-4(5-chloro-2-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate (3-2) as an orange oil. 1H NMR (300 MHz, CDCl3) major rotamer: δ 7.11-6.53 (m, 7H), 6.11 (s, 1H), 5.32 (m, 1H), 4.53 (m, 2H), 1.09 (s, 9H), 0.79 (s, 9H), 0.00 (s, 6H). LRMS m/z (M+H) 504.1 found, 504.2 required.

Workup

  1. customThe reaction mixture was partitioned between water (100 mL) and ethyl acetate (2×85 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography (100% hexanes initially

Sources & evidence

ORD record
ord-b184480e084541b9908f3929904a0a10
Source dataset
uspto-grants-2008_02
Patent number
US07329762B2

Linked notes

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