Lithium diisopropylamide → (S)-5,11-Dihydro-5-(1-[4-methylphenylsulphonyl]-2-pyrrolidinylmethyl)dibenzo[b,e][1,4]thiazepine

HRID 1460489Notes

Reaction equation

HRID 1460489 reaction equation
C([N-]C(C)C)(C)C.[Li+].COC1C=CC(CCN2CCC[C@H]2C[N:23]2[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[CH2:27][S:26][C:25]3[CH:34]=[CH:35][CH:36]=[CH:37][C:24]2=3)=CC=1.[CH3:40][C:41]1[CH:46]=[CH:45][C:44]([S:47]([N:50]2[CH2:54][CH2:53][CH2:52][C@H:51]2[CH2:55]OS(C2C=CC(C)=CC=2)(=O)=O)(=[O:49])=[O:48])=[CH:43][CH:42]=1>CCCCCC.COCCOC>[CH3:40][C:41]1[CH:42]=[CH:43][C:44]([S:47]([N:50]2[CH2:54][CH2:53][CH2:52][C@H:51]2[CH2:55][N:23]2[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[CH2:27][S:26][C:25]3[CH:34]=[CH:35][CH:36]=[CH:37][C:24]2=3)(=[O:48])=[O:49])=[CH:45][CH:46]=1

Participants

6

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 9824029(S)-5,11-Dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]thiazepineHCID 10905672{(2S)-1-[(4-methylphenyl)sulfonyl]pyrrolidin-2-yl}methyl 4-methylbenzenesulfonate

Product 1

HCID 22841645(S)-5,11-Dihydro-5-(1-[4-methylphenylsulphonyl]-2-pyrrolidinylmethyl)dibenzo[b,e][1,4]thiazepineYield 88.9%

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Lithium diisopropylamide (4.3 ml of a 1.5M solution in hexane) was added to a solution of 5,11-dihydrodibenzo[b,e][1,4]thiazepine (see Example 1 for source) (1.0 g) in DME (25 ml) and the mixture stirred at room temperature for 15 minutes, treated with (S)-1-(4-methylphenylsulphonyl)-2-(4-methylphenylsulphonyloxymethyl)pyrrolidine (3.9 g) (prepared by the method of P. Karrer and K. Ehrhardt, Helv. Chim. Acta, 34, 2202 (1951)), heated under reflux for 2.5 hours, allowed to cool to room temperature, quenched with 2M hydrochloric acid and extracted with ethyl acetate. The organic extract was washed with water, dried over sodium sulphate and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, performing a gradient elution initially using hexane as eluant and changing to hexane/ethyl acetate (90:10). Appropriate fractions were combined and evaporated under reduced pressure to give the title compound as a colourless solid, (0.93 g, 44%), m.p. 88°-90° C., [α]589 25 -115° (c=0.62 in ethanol).

Workup

  1. customprepared by the method of P
  2. temperatureActa, 34, 2202 (1951)), heated
  3. temperatureunder reflux for 2.5 hours
  4. temperatureto cool to room temperature
  5. customquenched with 2M hydrochloric acid
  6. extractionextracted with ethyl acetate
  7. extractionThe organic extract
  8. washwas washed with water
  9. dry with materialdried over sodium sulphate
  10. customevaporated under reduced pressure
  11. customThe residue was purified by chromatography on silica gel
  12. washa gradient elution initially using hexane as eluant
  13. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-a5135c786e1445139372059a6deba598
Source dataset
uspto-grants-1991_12
Patent number
US05071844

Reaction notes

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