4-Chlorobenzoic Acid → HCID 68692226, compound

HRID 1991485Notes

Reaction equation

HRID 1991485 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=O)=[CH:4][CH:3]=1.[CH:11]1([CH:17]=O)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.[CH:19]1([N+:25]#[C-:26])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.C(OC(=O)[NH:32][C:33]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=1[NH2:40])C=C.N1CC[O:45]CC1>CO>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]2[N:40]([CH:17]([CH:11]3[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]3)[C:26]([NH:25][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[O:45])[C:34]3[CH:35]=[CH:36][C:37]([F:39])=[CH:38][C:33]=3[N:32]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 63184-Chlorobenzoic AcidHCID 8083MorpholineHCID 16275CyclohexanecarboxaldehydeHCID 79129Cyclohexyl isocyanideHCID 68692451HCID 68692451, compound

Product 1

HCID 68692226HCID 68692226, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-Chlorobenzoic acid (156.6 mg, 1 mmol, 1 equiv.) was added to a solution of cyclohexanecarbaldehyde (168.3 mg, 1.5 mmol, 1.5 equiv.), cyclohexyl isocyanide (109.2 g, 1 mmol, 1 equiv.) and (2-amino-5-fluoro-phenyl)-carbamic acid allyl ester (210.2 mg, 1 mmol, 1 equiv.) in methanol (15 mL) and the mixture was stirred at room temperature for 16 hours. The solvent was evaporated and the crude product extracted from ethyl acetate and aq. NaHCO3. After separation of the organic layer and evaporation of the solvent, the residue was taken up in Acetonitril. Morpholine (435.5 mg. 5 mmol, 5 equiv.) and etrakis(triphenylphosphine)palladium (231.1 mg, 0.2 mmol, 0.2 equiv.) were added and the mixture stirred at room temperature for 3 hours. The solvent was evaporated and the crude product extracted from ethyl acetate and aq. NaHCO3. After separation of the organic layer and evaporation of the solvent, the residue was taken up in acetic acid. The mixture was stirred at 80° C. for 16 hours. The solvent was evaporated and the product isolated via preperative HPLC. MS (ES+): 469 (M+H).

Workup

  1. customThe solvent was evaporated
  2. extractionthe crude product extracted from ethyl acetate and aq. NaHCO3
  3. customAfter separation of the organic layer and evaporation of the solvent
  4. stirringthe mixture stirred at room temperature for 3 hours
  5. customThe solvent was evaporated
  6. extractionthe crude product extracted from ethyl acetate and aq. NaHCO3
  7. customAfter separation of the organic layer and evaporation of the solvent
  8. stirringThe mixture was stirred at 80° C. for 16 hours
  9. customThe solvent was evaporated
  10. customthe product isolated via preperative HPLC

Sources & evidence

ORD record
ord-e2f02c6add904d6f907bcf2b18641d0f
Source dataset
uspto-grants-2010_01
Patent number
US07645785B2

Reaction notes

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