4-Chloro-3-Fluorobenzaldehyde → 6-chloro-7-fluoro-1H-indole
Reaction equation
[Na].[N:2]([C:5](=[CH:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=1)C(OC)=O)=[N+]=[N-].ClC1C=CC(C=O)=CC=1F.N(CC(OC)=O)=[N+]=[N-]>CO>[Cl:17][C:14]1[C:13]([F:18])=[C:12]2[C:11]([CH:10]=[CH:5][NH:2]2)=[CH:16][CH:15]=1Participants
Conditions
- Temperature
- -15 °C
Procedure
Methyl 2-azido-3-(4-chloro-3-fluorophenyl)propenoate Sodium (2.32 g, 100 mmol) was added portionwise to stirred methanol (200 mL) at 0° C. under Ar. The mixture was stirred for 1 h and cooled to −15° C. A solution of 4-chloro-3-fluorobenzaldehyde (4.0 g, 25 mmol), methyl azidoacetate (8.7 g, 75 mmol) in methanol (20 mL) was added. The mixture was stirred for 3 h, warmed to 4° C. and stirred for 16 h and partitioned between water (300 mL) and ether (3×200 mL). The organic extracts were combined and washed with brine (2×), dried (magnesium sulfate) and concentrated in vacuo to give an orange solid. Recrystallisation (methanol) gave the product (5.09 g, 80% yield) as a pale yellow solid: IR νmax (Nujol)/cm−1 2115, 1708, 1616, 1234, 1060, 896, 818 and 616; NMR δH (400 MHz, CDCl3) 3.82 (3H, s) 6.64 (1H, s) 7.35-7.46 (2H, m) 7.74-7.78 (1H, m).
Workup
- stirringThe mixture was stirred for 3 h
- temperaturewarmed to 4° C.
- stirringstirred for 16 h
- custompartitioned between water (300 mL) and ether (3×200 mL)
- washwashed with brine (2×)
- dry with materialdried (magnesium sulfate)
- concentrationconcentrated in vacuo
- customto give an orange solid
- customRecrystallisation (methanol)
Sources & evidence
- ORD record
- ord-ee9fc87362564420ac2fca9a05627243
- Source dataset
- uspto-grants-2002_04
- Patent number
- US06380238B1
Reaction notes
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