Hydrochloric Acid → HCID 70621015, compound

HRID 372332Notes

Reaction equation

HRID 372332 reaction equation
[CH:1]([NH2:4])([CH3:3])[CH3:2].Cl.[CH2:6]([O:8][C:9]([C:11]1[N:12]([CH2:27][CH2:28][CH2:29][C:30](=O)[CH3:31])[C:13]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:14]2[C:19]=1[CH:18]=[CH:17][C:16]([Cl:20])=[CH:15]2)=[O:10])[CH3:7].C([BH3-])#N.[Na+]>CO>[ClH:20].[CH2:6]([O:8][C:9]([C:11]1[N:12]([CH2:27][CH2:28][CH2:29][CH:30]([NH:4][CH:1]([CH3:3])[CH3:2])[CH3:31])[C:13]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[C:14]2[C:19]=1[CH:18]=[CH:17][C:16]([Cl:20])=[CH:15]2)=[O:10])[CH3:7]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 6363IsopropylamineHCID 5003444Sodium cyanoborohydrideHCID 54533235HCID 54533235, compound

Product 1

HCID 70621015HCID 70621015, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 5.2 ml. of isopropylamine in 25 ml. of methanol is treated with 4 ml. of 5-N methanolic hydrochloric acid. To this there are added successively under an atmosphere of argon at 20°-25° C. 3.85 g. of 5-chloro-2-(4-oxopentyl)-3-phenylisoindole-1-carboxylic acid ethyl ester and 0.4 g. of sodium cyanoborohydride and the mixture is then stirred for 48 hours at room temperature. While cooling, the mixture is made acidic with concentrated hydrochloric acid, stirred for an additional 1 hour at room temperature and subsequently evaporated to dryness under reduced pressure. The residue is made alkaline with 1-N sodium hydroxide with addition of ice and is extracted with ether. The extract is dried over sodium sulfate, concentrated, and the oily residue chromatographed on 200 g. of silica gel with a mixture of ethyl acetate/tetrahydrofuran/triethylamine (40:10:1). The homogeneous fractions are combined, concentrated, dissolved in ether and treated with an excess of ethereal hydrochloric acid. The precipitated hydrochloride is removed by filtration and washed with ether. After recrystallization from acetone, there is obtained 5-chloro-2-[4-(isopropylamino)pentyl]-3-phenylisoindole-1-carboxylic acid ethyl ester hydrochloride having a melting point of 183°-185° C. (decomposition).

Workup

  1. additionTo this there are added successively under an atmosphere of argon at 20°-25° C
  2. temperatureWhile cooling
  3. customsubsequently evaporated to dryness under reduced pressure
  4. additionwith addition of ice
  5. extractionis extracted with ether
  6. dry with materialThe extract is dried over sodium sulfate
  7. concentrationconcentrated
  8. customthe oily residue chromatographed on 200 g
  9. additionof silica gel with a mixture of ethyl acetate/tetrahydrofuran/triethylamine (40:10:1)
  10. concentrationconcentrated
  11. dissolutiondissolved in ether
  12. additiontreated with an excess of ethereal hydrochloric acid
  13. customThe precipitated hydrochloride is removed by filtration
  14. washwashed with ether
  15. customAfter recrystallization from acetone

Sources & evidence

ORD record
ord-4b482c989d0b4d099ca6bbfe126b31ad
Source dataset
uspto-grants-1978_05
Patent number
US04090027

Reaction notes

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