Methyl trifluoroacetate → HCID 10183781, compound

HRID 857348Notes

Reaction equation

Br[C:2]1[C:3]2[C:4]([S:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)=[C:5]3[CH:14]([CH2:15][C:16]([OH:18])=[O:17])[CH2:13][CH2:12][N:6]3[C:7]=2[CH:8]=[C:9]([F:11])[CH:10]=1.C[Mg+].[Br-].[Li]C(CC)C.[F:35][C:36]([F:42])([F:41])[C:37](OC)=[O:38].[NH4+].[Cl-]>C1COCC1>[Cl:26][C:23]1[CH:22]=[CH:21][C:20]([S:19][C:4]2[C:3]3[C:2]([C:37](=[O:38])[C:36]([F:42])([F:41])[F:35])=[CH:10][C:9]([F:11])=[CH:8][C:7]=3[N:6]3[CH2:12][CH2:13][CH:14]([CH2:15][C:16]([OH:18])=[O:17])[C:5]=23)=[CH:25][CH:24]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of (+/−)-[8-bromo-9-[(4-chlorophenyl)sulfanyl]-6-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl]acetic acid (Example 7, 250 mg, 0.6 mmol) in THF (8 mL) at −78° C. was added 3M MeMgBr (0.7 mmol) followed by the addition of sec-BuLi (0.8 mmol, 1.3M solution). The reaction mixture was stirred at −78° C. for 5 minutes and methyl trifluoroacetate (352 mg, 2.8 mmol) was added., The reaction mixture was warmed to r.t., stirred for 4 hours and saturated aqueous NH4Cl was added. The phases were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with EtOAc/Hexanes/AcOH (20:30:1) to provide 150 mg of the title compound as a white solid.

Workup

temperature, The reaction mixture was warmed to r.t.
stirringstirred for 4 hours
customThe phases were separated
extractionthe aqueous layer was extracted with EtOAc
dry with materialThe combined organic layers were dried over Na2SO4
concentrationconcentrated
customThe residue was purified by silica gel chromatography
washeluted with EtOAc/Hexanes/AcOH (20:30:1)

Sources & evidence

ORD record: ord-3e4f7d8f4a3d4592a05ea37641c79870
Source dataset: uspto-grants-2006_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07144913B2

Reaction notes

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