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

HRID 1033481Notes

Reaction equation

HRID 1033481 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>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

6

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 83.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of L-tert-leucine (721 mg), sodium borohydride (189 mg) and tetrahydrofuran (25 ml) is refluxed under nitrogen atmosphere for three hours. The mixture is cooled to room temperature, and thereto is added tetrahydrofuran (25 ml). The mixture is cooled to -30° C., and thereto is added 2-(4-methoxyphenyl)-1,5-benzothiazepine-3,4(2H,5H)-dione (997 mg). Each 139 μl of conc. hydrochloric acid (1.67 mmole as hydrogen chloride) is added at 1, 3, 5 and 22 hours after the beginning of the reaction, and the reaction is carried out for 45 hours. After confirming by HPLC that the starting compound is completely consumed, the mixture is evaporated under reduced pressure to remove the solvent, and water (70 ml) is added to the residue. The mixture is stirred at room temperature for one hour, and the precipitated crystal is collected by filtration and dried. The resulting residue is suspended in isopropyl alcohol (13 ml), and the mixture is refluxed for one hour. The mixture is cooled to 5° C., and allowed to stand overnight. The precipitated crystal is collected by filtration, and washed with cold isopropyl alcohol, and dried to give (2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (842 mg).

Workup

  1. temperatureis refluxed under nitrogen atmosphere for three hours
  2. temperatureThe mixture is cooled to -30° C.
  3. customafter the beginning of the reaction
  4. customis completely consumed
  5. customthe mixture is evaporated under reduced pressure
  6. customto remove the solvent, and water (70 ml)
  7. additionis added to the residue
  8. filtrationthe precipitated crystal is collected by filtration
  9. customdried
  10. temperaturethe mixture is refluxed for one hour
  11. temperatureThe mixture is cooled to 5° C.
  12. waitto stand overnight
  13. filtrationThe precipitated crystal is collected by filtration
  14. washwashed with cold isopropyl alcohol
  15. customdried

Sources & evidence

ORD record
ord-3c6e998913bc41a587e3e6cee9fa5526
Source dataset
uspto-grants-1994_05
Patent number
US05310904

Reaction notes

Loading…