4-Bromo-3-fluorophenol → (1S,2R)-2-(4-Bromo-3-fluorophenoxy)cyclohexanamine

HRID 2360312Notes

Reaction equation

HRID 2360312 reaction equation
BrC1C=CC(O[C@H]2CCC[C@H]2N[S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])=CC=1.[Br:21][C:22]1[CH:35]=[CH:34][C:25]([O:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C@@H:28]2[NH2:33])=[CH:24][C:23]=1[F:36].BrC1C=CC(O[C@@H]2CCCC[C@@H]2N)=CC=1.BrC1C=CC(O)=CC=1F>>[Br:21][C:22]1[CH:35]=[CH:34][C:25]([O:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C@@H:28]2[NH2:33])=[CH:24][C:23]=1[F:36].[Br:21][C:22]1[CH:35]=[CH:34][C:25]([O:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][CH2:29][C@@H:28]2[NH:33][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])=[CH:24][C:23]=1[F:36]

Participants

6

Reactant 4

HCID 27791534-Bromo-3-fluorophenolHCID 67193989cis-N-[2-(4-bromophenoxy)cyclopentyl]propane-2-sulfonamideHCID 67194497(1S,2R)-2-(4-Bromo-3-fluorophenoxy)cyclohexanamineHCID 67198839(1S,2R)-2-(4-bromophenoxy)cyclohexanamine

Product 2

HCID 67194497(1S,2R)-2-(4-Bromo-3-fluorophenoxy)cyclohexanamineHCID 67197079N-[(1S,2R)-2-(4-bromo-3-fluorophenoxy)cyclohexyl]propane-2-sulfonamide

Procedure

The title compound was prepared according to the general procedure for the synthesis of cis-N-[2-(4-bromophenoxy)cyclopentyl]propane-2-sulfonamide in Example 5, except that (1S,2R)-2-(4-bromo-3-fluorophenoxy)cyclohexanamine was used in place of cis-2-(4-bromophenoxy)cyclopentanamine, and the chromatographic purification employed 0% to 1% methanol in dichloromethane as gradient. (1S,2R)-2-(4-Bromo-3-fluorophenoxy)cyclohexanamine was synthesized according to the general procedures described for synthesis of (1S,2R)-2-(4-bromophenoxy)cyclohexanamine in Example 7, except for the use of 4-bromo-3-fluorophenol in place of 4-bromophenol. The title compound was obtained as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.33-1.53 (m, 4H), 1.35-1.38 (m, 6H), 1.78-1.89 (m, 3H), 2.04-2.10 (m, 1H), 3.12 (septet, J=6.8 Hz, 1H), 3.54 (m, 1H), 4.44 (d, J=9.6 Hz, 1H), 4.55 (m, 1H), 6.67 (br dd, J=8.9, 2.8 Hz, 1H), 6.75 (dd, J=10.2, 2.7 Hz, 1H), 7.43 (dd, J=8.5, 8.5 Hz, 1H). The absolute configuration of the title compound was established via X-ray crystallography.

Workup

  1. customThe title compound was prepared
  2. customthe chromatographic purification

Sources & evidence

ORD record
ord-986fb3f2ad6b4c258019e0edeb4c99c2
Source dataset
uspto-grants-2014_04
Patent number
US08686043B2

Reaction notes

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