Phenol → HCID 67436641, compound

HRID 446952Notes

Reaction equation

HRID 446952 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.C1(O)C=CC=CC=1.[C:20]12([NH:30]CCCN)[CH2:29][CH:24]3[CH2:25][CH:26]([CH2:28][CH:22]([CH2:23]3)[CH2:21]1)[CH2:27]2.[NH2:35][C:36]12CC3CC(C[CH:38](C3)[CH2:37]1)C2.ClC1C=C2C(C(NC34CC5CC(CC(C5)C3)C4)=CC=N2)=CC=1.[OH-].[K+]>CO>[Cl:12][C:8]1[CH:7]=[C:6]2[C:11]([CH:2]=[C:3]([NH:30][C:20]34[CH2:27][CH:26]5[CH2:25][CH:24]([CH2:23][CH:22]([CH2:28]5)[CH2:21]3)[CH2:29]4)[C:4]([CH2:38][CH2:37][CH2:36][NH2:35])=[N:5]2)=[CH:10][CH:9]=1

Participants

8

Reactant 6

HCID 996PhenolHCID 2130AmantadineHCID 68664,7-Dichloroquinoline2×HCID 14797Potassium HydroxideHCID 5032001N1-Tricyclo[3.3.1.13,7]dec-1-yl-1,3-propanediamineHCID 10495357HCID 10495357, compound

Product 1

HCID 67436641HCID 67436641, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4.7-dichloroquinoline (0.29 g), 1 g of phenol and 0.6 g of impure (containing 1-aminoadamantane) 3-adamantylaminopropylamine were heated at 120° C. for 3 hours. By g.c-m.s. analysis it was found that the mixture contained besides the aimed—at product, 1-aminoadamantane, some 4.7-dichloroquinoline and a product which is by its mass spectrum 7-chloro-4-adamantylaminoquinoline (M+=312.5). The mixture was dissolved in several ml of methanol, poured into 50 ml of 10% KOH and extracted with t-butyl methyl ether (2×50 ml). The combined extracts were brought to dryness, the residue dissolved in a mixture of N(C2H5)3, little (CH3)3COCH3 and some methanol, transferred to a column (5 cm. diameter, Kieselgel, wetted with N(C2H5)3: (CH3)3OCH3: CH3OH=125:75:5 (by volume) and eluted with 205 ml of this solvent. The solvent was changed to N(C2H5)3: (CH3)3OCH3:CH3OH=100:100:10 (by volume), and the product together with M+=151 (adamantylamine) was eluted, +another by-product (by g.c.-m.s. perhaps 7-chloroquinolone, which was not in the crude product prior to base-treatment). After re-elution (30 g Kieselgel, N(C2H5)3: CH3OH=200:5, fraction collection and their g.c-m.s. analysis), 33 mg of pure 7-chloro-(3-adamantylamino)-aminopropylquinoline was obtained as a white solid. Yield=6% of theory. G.c.-m.s. (DB5-column, 30 m, injection block temperature=250° C., t0=150° C./2 min, then 11° C./min.→280° C., Rt=24.05 min.): M(35Cl, 37Cl)+=369 (24%), 371 (9%), 135, C10H15+, (100%).

Workup

  1. extractionextracted with t-butyl methyl ether (2×50 ml)
  2. dissolutionthe residue dissolved in a mixture of N(C2H5)3, little (CH3)3COCH3
  3. wash(CH3)3OCH3: CH3OH=125:75:5 (by volume) and eluted with 205 ml of this solvent
  4. wash(CH3)3OCH3:CH3OH=100:100:10 (by volume), and the product together with M+=151 (adamantylamine) was eluted
  5. washAfter re-elution (30 g Kieselgel, N(C2H5)3: CH3OH=200:5, fraction collection and their g.c-m.s. analysis)

Sources & evidence

ORD record
ord-b1bf7ad999434345a0f0b38dd502f406
Source dataset
uspto-grants-2013_07
Patent number
US08481543B2

Reaction notes

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