4-Chlorobenzaldehyde → 5-bromo-2-[(4-chloro-phenyl)-hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester

HRID 2204299Notes

Reaction equation

[Li+].CC([N-]C(C)C)C.[CH3:9][O:10][C:11]([C:13]1[CH:17]=[C:16]([Br:18])[N:15]([CH:19]([CH3:21])[CH3:20])[CH:14]=1)=[O:12].[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[CH:25][CH:24]=1>C1COCC1>[CH3:9][O:10][C:11]([C:13]1[CH:17]=[C:16]([Br:18])[N:15]([CH:19]([CH3:21])[CH3:20])[C:14]=1[CH:27]([C:26]1[CH:29]=[CH:30][C:23]([Cl:22])=[CH:24][CH:25]=1)[OH:28])=[O:12]

Participants

Conditions

Temperature: -20 °C

Procedure

LDA (6.20 mmol) was added dropwise to a solution of 5-bromo-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester (Step D4) (2.066 mmol) in THF (15 mL) at −78° C. and the mixture was stirred for 2 h. A solution of 4-chlorobenzaldehyde [104-88-1] (6.20 mmol) in THF (5 mL) was added and the mixture was stirred for 1 h. The mixture was warmed to −20° C., quenched with HOAc and stirred at rt overnight. The reaction mixture was diluted with H2O and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified using a RediSep® silica gel column to afford the title compound as an off-white solid. tR: 5.57 min (HPLC 1); ESI-MS: tR=1.36 min, [M+H]+ 368/370/372 (LC-MS 1); TLC: Rf=0.23 (1:6 EtOAc/heptanes).

Workup

stirringthe mixture was stirred for 1 h
customquenched with HOAc
stirringstirred at rt overnight
additionThe reaction mixture was diluted with H2O
extractionextracted with EtOAc (3×)
washThe combined organic layers were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified

Sources & evidence

ORD record: ord-b32f31a82f024828aa8e9decca9f7fc1
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365576B2

Reaction notes

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