Ammonia → 4-[5-[4-(aminoiminomethyl)phenoxy]pentoxy]-3-methoxy-N,N-bis(1-methylethyl)benzamide

HRID 2399945Notes

Reaction equation

HRID 2399945 reaction equation
[CH2:1]([OH:3])C.Cl.CO[C:7]1[CH:8]=[C:9]([CH:28]=[CH:29][C:30]=1[C:31]([N:33]([CH:37]([CH3:39])[CH3:38])[CH:34]([CH3:36])[CH3:35])=[O:32])[O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([C:23](=[NH:27])OCC)=[CH:19][CH:18]=1.[NH3:40].Cl>O.C(Cl)Cl.CO>[NH2:40][N:27]=[CH:23][C:20]1[CH:19]=[CH:18][C:17]([O:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][O:10][C:9]2[CH:8]=[CH:7][C:30]([C:31]([N:33]([CH:37]([CH3:39])[CH3:38])[CH:34]([CH3:35])[CH3:36])=[O:32])=[CH:29][C:28]=2[O:3][CH3:1])=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 222Ammonia2×HCID 313Hydrochloric AcidHCID 702EthanolHCID 18991643ethyl 4-[5-[3-methoxy-4-[N,N-bis(1-methylethyl)aminocarbonyl]phenoxy]pentoxy]benzenecarboximidoate monohydrochloride

Product 1

HCID 1838004-[5-[4-(aminoiminomethyl)phenoxy]pentoxy]-3-methoxy-N,N-bis(1-methylethyl)benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
5 °C

Procedure

Ethanol 2 B (42 L) is added to the reactor and the ethyl 4-[5-[3-methoxy-4-[N,N-bis(1-methylethyl)aminocarbonyl]phenoxy]-pentoxy]benzenecarboximidoate monohydrochloride is dissolved. The solution is cooled to 5° C. and anhydrous ammonia is bubbled into the solution for 7.5 hours until saturation is obtained. After stirring overnight in the ice bath, and ammonia addition is continued another 7.5 hours at 5° C. The reaction mixture is followed by TLC (CH2Cl2 /MeOH, 9:1) using silica plates. A total of four days is required for completion of reaction with periodic resaturation with ammonia gas. The reaction mixture is filtered and the filtrate divided into two equal portions. Concentration in vacuo (55° C., 3 mm Hg) gives an oily viscous suspension which is charged into a 20 gallon reactor. This is admixed with hydrochloric acid (12 N, 560 ml), diluted with water (44 L). At this point, the compound dissolves (pH is 1.62). The solution is washed with diethyl ether (3×18 L), and the pH adjusted to 12.6 with a 6 N sodium hydroxide solution (3.0 L). The oily suspension crystallizes after stirring overnight at 20° C. The product is filtered, washed with water (5×4 L) and dried in vacuo (60° C. 3 mm Hg) to give the product. The second half of the reaction mixture is worked up in a similar manner to give 4-[5-[4-(aminoiminomethyl)phenoxy]pentoxy]-3-methoxy-N,N-bis(1-methylethyl)-benzamide is obtained, mp 112°-114° C. HPLC indicates a purity of 98.5%.

Workup

  1. customanhydrous ammonia is bubbled into the solution for 7.5 hours until saturation
  2. customis obtained
  3. filtrationThe reaction mixture is filtered
  4. concentrationConcentration in vacuo (55° C., 3 mm Hg)
  5. customgives an oily viscous suspension which
  6. additionis charged into a 20 gallon reactor
  7. dissolutionAt this point, the compound dissolves (pH is 1.62)
  8. washThe solution is washed with diethyl ether (3×18 L)
  9. customThe oily suspension crystallizes
  10. filtrationThe product is filtered
  11. washwashed with water (5×4 L)
  12. customdried in vacuo (60° C. 3 mm Hg)
  13. customto give the product

Sources & evidence

ORD record
ord-72f6d65bb7bd4d6f8072f2152cd14357
Source dataset
uspto-grants-1995_09
Patent number
US05451700

Reaction notes

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