Dimethylformamide dimethyl acetal → 4-fluoro-1H-indol-5-ol

HRID 1971328Notes

Reaction equation

HRID 1971328 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[C:11]([CH3:18])[C:10]=1[F:19])C1C=CC=CC=1.[CH3:20]OC(OC)N(C)C>[Pd]>[F:19][C:10]1[C:9]([OH:8])=[CH:14][CH:13]=[C:12]2[C:11]=1[CH:18]=[CH:20][NH:15]2

Participants

4

Reactant 2

HCID 78373Dimethylformamide dimethyl acetalHCID 59394770HCID 59394770, compound

Product 1

HCID 220305534-fluoro-1H-indol-5-olYield 52%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Conditions

Temperature
180 °C

Procedure

1-Benzyloxy-2-fluoro-3-methyl-4-nitrobenzene (5 g, 19 mmol) is dissolved N,N-dimethylformamide dimethyl acetal (15 mL) and heated in a microwave reactor at 180° C. in a sealed vial for 1 hour. The solution is then concentrated under reduced pressure. The resulting residue is dissolved in THF and Pd/C (1.0 g, 10%, 0.95 mmol) is added. The mixture is stirred under a hydrogen atmosphere at room temperature for 16 h before being filtered through a pad of Celite® and concentrated. The residue is separated by FCC (EtOAc/heptane from 0 to 40%) to give 4-fluoro-1H-indol-5-ol (1.5 g, 52% yield). MS (ESI) m/z 152.1 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.02 (br. s., 1 H), 8.79 (s, 1 H), 7.26 (t, J=2.78 Hz, 1 H), 7.00 (d, J=8.59 Hz, 1 H), 6.75 (t, J=8.46 Hz, 1 H), 6.34 (m, 1 H).

Workup

  1. concentrationThe solution is then concentrated under reduced pressure
  2. dissolutionThe resulting residue is dissolved in THF
  3. filtrationbefore being filtered through a pad of Celite®
  4. concentrationconcentrated
  5. customThe residue is separated by FCC (EtOAc/heptane from 0 to 40%)

Sources & evidence

ORD record
ord-c19b6baa9bbb48888951caebc8a45c71
Source dataset
uspto-grants-2013_04
Patent number
US08431584B2

Reaction notes

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