2-Chloro-4-fluorobenzoyl chloride → HCID 69350991, compound

HRID 970743Notes

Reaction equation

HRID 970743 reaction equation
[CH3:1][N:2]([CH3:17])[CH:3]1[CH2:8][CH2:7][C:6]([C:9]2[CH:10]=[C:11]([NH2:16])[CH:12]=[C:13]([F:15])[CH:14]=2)=[CH:5][CH2:4]1.[Cl:18][C:19]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:20]=1[C:21](Cl)=[O:22]>O1CCOCC1>[ClH:18].[Cl:18][C:19]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:20]=1[C:21]([NH:16][C:11]1[CH:12]=[C:13]([F:15])[CH:14]=[C:9]([C:6]2[CH2:7][CH2:8][CH:3]([N:2]([CH3:17])[CH3:1])[CH2:4][CH:5]=2)[CH:10]=1)=[O:22]

Participants

4

Reactant 2

HCID 27365462-Chloro-4-fluorobenzoyl chlorideHCID 58852362HCID 58852362, compound

Product 1

HCID 69350991HCID 69350991, compoundYield 99.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Combine chiral 3-(4-dimethylamino-cyclohex-1-enyl)-5-fluoro-phenylamine (isomer 5A, preparation 5, 0.25 g, 1.07 mmol), 2-chloro-4-fluoro-benzoyl chloride (0.31 g, 1.6 mmol) and 1,4-dioxane (5 mL) and heat to reflux for 3 hr. Cool to ambient temperature and remove volatiles. Purify the residue by flash chromatography (silica gel, 10% 2M NH3/MeOH in DCM) to obtain the free base of the title compound (0.34 g, 81%). Convert to the hydrochloride salt by dissolving in ether and treating with 1M HCl in ether: MS (ES) m/z=391 (M+H)+; 1H NMR of free base (CDCl3): δ 8.19 (s, 1H), 7.72 (m, 1H), 7.42 (d, 1H, J=10 Hz), 7.26 (s, 1H), 7.16 (m, 1H), 7.06 (m, 1H), 6.86 (d, 1H, J=10 Hz), 6.09 (bs, 1H), 2.40 (m, 4H), 2.32 (s, 6H), 2.11 (m, 2H), 1.53 (m, 1H).

Workup

  1. temperatureto reflux for 3 hr
  2. customremove volatiles
  3. customPurify the residue by flash chromatography (silica gel, 10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-fc5bef67fbe04d5992709881100453a1
Source dataset
uspto-grants-2007_12
Patent number
US07312236B2

Reaction notes

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