Hydrochloric Acid → 3-Hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, (2S,3S)-

HRID 1033474Notes

Reaction equation

HRID 1033474 reaction equation
N[C@H](C(O)=O)C(C)(C)C.[BH4-].[Na+].[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]2[C:26](=[O:27])[C:25](=[O:28])[NH:24][C:23]3[CH:29]=[CH:30][CH:31]=[CH:32][C:22]=3[S:21]2)=[CH:16][CH:15]=1.Cl>C(OCC)(=O)C.O1CCCC1>[OH:27][C@H:26]1[C:25](=[O:28])[NH:24][C:23]2[CH:29]=[CH:30][CH:31]=[CH:32][C:22]=2[S:21][C@H:20]1[C:17]1[CH:18]=[CH:19][C:14]([O:13][CH3:12])=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 164608L-tert-LeucineHCID 4311764Sodium borohydrideHCID 109026231,5-Benzothiazepine-3,4(2H,5H)-dione, 2-(4-methoxyphenyl)-

Product 1

HCID 27336733-Hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, (2S,3S)-Yield 62.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-15 °C

Procedure

A mixture of L-tert-leucine (393 mg), sodium borohydride (98 mg) and tetrahydrofuran (100 ml) is refluxed under nitrogen atmosphere for three hours. The mixture is cooled to -15° C., and thereto is added 2-(4-methoxyphenyl)-1,5-benzothiazepine-3,4(2H,5H)-dione (599 mg), and the mixture is further stirred at -15° C. for 48 hours. To the reaction solution are added 1N hydrochloric acid (10 ml) and ethyl acetate (20 ml), and the mixture is stirred for 30 minutes. The organic layer is separated, washed with water, dried, and evaporated under reduced pressure to remove the solvent. The resulting residue is dissolved in ethanol (22 ml) with heating, and the mixture is cooled gradually for crystallization. The precipitated crystal is collected by filtration to give (2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (376 mg).

Workup

  1. temperatureis refluxed under nitrogen atmosphere for three hours
  2. stirringthe mixture is stirred for 30 minutes
  3. customThe organic layer is separated
  4. washwashed with water
  5. customdried
  6. customevaporated under reduced pressure
  7. customto remove the solvent
  8. dissolutionThe resulting residue is dissolved in ethanol (22 ml)
  9. temperaturewith heating
  10. temperaturethe mixture is cooled gradually for crystallization
  11. filtrationThe precipitated crystal is collected by filtration

Sources & evidence

ORD record
ord-28c756f20f51470485991380156034fe
Source dataset
uspto-grants-1994_05
Patent number
US05310904

Reaction notes

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