4-Fluorophenol → HCID 59262242, compound
Reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]([CH3:33])[C:11]2[CH:16]=[CH:15][C:14]([CH2:17][N:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:20]([CH3:31])[CH2:19]3)=[CH:13][C:12]=2[F:32])=[O:9])=[CH:4][CH:3]=1.[F:34][C:35]1[CH:40]=[CH:39][C:38]([OH:41])=[CH:37][CH:36]=1.C(=O)([O-])[O-].[K+].[K+]>>[F:32][C:12]1[CH:13]=[C:14]([CH2:17][N:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@@H:20]([CH3:31])[CH2:19]2)[CH:15]=[CH:16][C:11]=1[N:10]([C:8]([C:5]1[CH:6]=[N:7][C:2]([O:41][C:38]2[CH:39]=[CH:40][C:35]([F:34])=[CH:36][CH:37]=2)=[CH:3][CH:4]=1)=[O:9])[CH3:33]Participants
Conditions
- Temperature
- 130 °C
Procedure
The title compound was prepared from 1,1-dimethylethyl (2S)-4-({4-[[(6-chloro-3-pyridinyl)carbonyl](methyl)amino]-3-fluorophenyl}methyl)-2-methyl-1-piperazinecarboxylate (D68) and 4-fluorophenol using a method similar to that described for D55 in Description 55 although only 1 eq of 4-fluorophenol was added initially, the reaction was heated at 130° C. over-weekend, further 4-fluorophenol (2 eq) and potassium carbonate (4 eq) were added and the reaction was heated at 130° C. overnight. The product was purified by column chromatography. δH (CDCl3, 400 MHz) 8.07 (1H, s), 7.73 (1H, dd), 7.04 (7H, m), 6.74 (1H, d), 4.19 (1H, br.s), 3.80 (1H, d), 3.43 (4H, m), 3.33 (1H, d), 3.08 (1H, td), 2.67 (1H, d), 2.49 (1H, d), 2.13 (1H, dd), 2.00 (1H, m), 1.45 (9H, s), 1.21 (3H, d).
Workup
- additionwas added initially
- temperaturethe reaction was heated at 130° C. overnight
- customThe product was purified by column chromatography
Sources & evidence
- ORD record
- ord-c80e16c441614c11a88dc859f4bcaebc
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08853218B2
Reaction notes
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