2-Methyl-2-butene → 6-fluoro-5-[4-(hydroxymethyl)phenyl]-1H-indole-3-carboxylic acid

HRID 338234Notes

Reaction equation

[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH2:19][OH:20])=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:27].[Na+].O.P([O-])(O)(O)=O.[Na+]>C(#N)C.C(O)(C)(C)C.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:27])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH2:19][OH:20])=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 6-fluoro-5-[4-(hydroxymethyl)phenyl]-1H-indole-3-carbaldehyde (65 mg, 0.24 mmol) in acetonitrile (3 mL) and tert-butanol (3 mL) was treated with 2-methyl-2-butene (2 mL, 18.4 mmol) and cooled to 0° C. A solution of sodium chlorite (410 mg, 4.9 mmol) and sodium dihydrogen phosphate monohydrate (684 mg, 4.96 mmol) in water (3 mL) was added dropwise via an addition funnel. The reaction mixture was warmed to room temperature and stirred for 65 hours. The reaction was partially evaporated in vacuo, and partitioned between water and ethyl acetate. The organic phase was concentrated in vacuo. The crude material was purified using reverse-phase chromatography to give the title compound (20.4 mg).

Workup

temperatureThe reaction mixture was warmed to room temperature
customThe reaction was partially evaporated in vacuo
custompartitioned between water and ethyl acetate
concentrationThe organic phase was concentrated in vacuo
customThe crude material was purified

Sources & evidence

ORD record: ord-f87324e8a05b4325b2b6cb578d757ebb
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889730B2

Reaction notes

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