L-tert-Leucine → (+)-cis-2-(4-methoxyphenyl)-3-hydroxy-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-one

HRID 1033479Notes

Reaction equation

HRID 1033479 reaction equation
N[C@H](C(O)=O)C(C)(C)C.[BH4-].[Na+].[Cl:12][C:13]1[CH:33]=[CH:32][C:16]2[NH:17][C:18](=[O:31])[C:19](=[O:30])[CH:20]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[S:21][C:15]=2[CH:14]=1.C(O)(=O)C.O1CCCC1>O1CCCC1>[Cl:12][C:13]1[CH:33]=[CH:32][C:16]2[NH:17][C:18](=[O:31])[C@H:19]([OH:30])[C@H:20]([C:22]3[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=3)[S:21][C:15]=2[CH:14]=1

Participants

6

Reactant 4

HCID 164608L-tert-LeucineHCID 4311764Sodium borohydrideHCID 15235733HCID 15235733, compoundHCID 23444217Acetic acid tetrahydrofuran

Product 1

HCID 15593400(+)-cis-2-(4-methoxyphenyl)-3-hydroxy-8-chloro-2,3-dihydro-1,5-benzothiazepin-4(5H)-oneYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-15 °C

Procedure

A mixture of L-tert-leucine (721 mg), sodium borohydride (189 mg) and tetrahydrofuran (50 ml) is refluxed under nitrogen atmosphere for three hours. The mixture is cooled to -15° C., and thereto is added 8-chloro-2-(4-methoxyphenyl)-1,5-benzothiazepine-3,4(2H,5H)-dione (1113 mg). Each 0.38 ml of 25% acetic acid/tetrahydrofuran solution (1.67 mole as acetic acid) is added thereto at 20 minutes, and 2 hours 20 minutes after the beginning of the reaction, and the reaction solution is stirred at the same temperature for 19 hours. The mixture is evaporated under reduced pressure to remove the solvent, and to the residue is added 1N hydrochloric acid (70 ml). The precipitated crystal is collected by filtration, washed with water, and dried. The collected crystal is suspended in chloroform (50 ml), and the mixture is heated with stirring at 65° C. The mixture is cooled to 5° C., and allowed to stand overnight. The precipitated crystal is collected by filtration, and dried to give (2S,3S)-8-chloro-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (896 mg).

Workup

  1. temperatureis refluxed under nitrogen atmosphere for three hours
  2. custom2 hours 20 minutes after the beginning of the reaction
  3. customThe mixture is evaporated under reduced pressure
  4. customto remove the solvent
  5. additionto the residue is added 1N hydrochloric acid (70 ml)
  6. filtrationThe precipitated crystal is collected by filtration
  7. washwashed with water
  8. customdried
  9. temperaturethe mixture is heated
  10. stirringwith stirring at 65° C
  11. temperatureThe mixture is cooled to 5° C.
  12. waitto stand overnight
  13. filtrationThe precipitated crystal is collected by filtration
  14. customdried

Sources & evidence

ORD record
ord-2b2d6ac094084cf3836584f6733b31d6
Source dataset
uspto-grants-1994_05
Patent number
US05310904

Reaction notes

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