Diisopropylamine → HCID 131721066, compound

HRID 342198Notes

Reaction equation

HRID 342198 reaction equation
C(N(C)CCCCCC[O:11][C:12]1[CH:21]=[CH:20][C:15]2[C:16](C)=[N:17][S:18][C:14]=2[CH:13]=1)C=C.C([N-][CH:27]([CH3:29])[CH3:28])(C)C.[Li+].C([NH:34]C(C)C)(C)C.[CH2:38]([Li])[CH2:39][CH2:40][CH3:41].[CH3:43][C:44]([CH3:48])=[CH:45][CH2:46]Br>C1COCC1.CCOCC.C(O)(=O)C>[CH3:43][C:44]([CH3:48])=[CH:45][CH2:46][CH2:41][CH:40]([CH2:29][CH2:27][CH3:28])[CH2:39][CH2:38][NH:34][O:11][C:12]1[CH:21]=[CH:20][C:15]2[CH:16]=[N:17][S:18][C:14]=2[CH:13]=1

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 700922-Butene, 1-bromo-3-methyl-HCID 2724682Lithium diisopropylamideHCID 67684926HCID 67684926, compoundHCID 178418339Butyllithium

Product 1

HCID 131721066HCID 131721066, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

105 mg of allyl-methyl-[6-(3-methyl-benzo[d]isothiazol-6-yloxy)-hexyl]-amine (Ex. 2d) in 2 ml of THF are added dropwise over a period of 20 min. at -78° C. to a lithium diisopropylamide (LDA) solution previously prepared from 100 μl of diisopropylamine and 425 μl of n-butyllithium (1.6M in hexane) in 2 ml of THF. The mixture is stirred at -78° C., treated with 3,3-dimethylallyl bromide and thawed overnight. For the working-up, the mixture is again cooled to -78° C. and treated with 42 μl of acetic acid in 0.3 ml of ether. The mixture is added to ice-cold sodium hydrogen carbonate solution and the inorganic phase is extracted with methylene chloride. The organic phases are washed with sodium chloride solution and dried. The crude product obtained after concentration is purified by column chromatography (silica gel, CH2Cl2 :MeOH:NH4OH 95:5:0.5). 63 mg of allyl-methyl-[6-[3-(4-methyl-pent-3-enyl)-benzo[d]isothiazol-6-yloxyl-hexyl-amine are obtained. This is taken up in 2 ml of ethanol and treated with 18.1 mg of fumaric acid. After stirring the solvent is removed and the residue is lyophilized. There are obtained 80 mg of allyl-methyl-[6-[3-(4-methyl-pent-3-enyl)-benzo[d]isothiazol-6-yloxy]-hexyl-amine.fumarate (1:1), MS: m/e 357 (M+H+).

Workup

  1. temperaturethe mixture is again cooled to -78° C.
  2. additionThe mixture is added to ice-cold sodium hydrogen carbonate solution
  3. extractionthe inorganic phase is extracted with methylene chloride
  4. washThe organic phases are washed with sodium chloride solution
  5. customdried
  6. customThe crude product obtained
  7. concentrationafter concentration
  8. customis purified by column chromatography (silica gel, CH2Cl2 :MeOH:NH4OH 95:5:0.5)

Sources & evidence

ORD record
ord-482822d3a7c047809e41674808f37c20
Source dataset
uspto-grants-1999_01
Patent number
US05856503

Reaction notes

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