Ethyl Acetate → (R)-2-(4-Chlorophenyl)-4-[(S)-N-(2-naphthalene-sulfonyl)prolyl]-3,4-dihydro-2H-1,4-benzothiazine

HRID 1198449Notes

Reaction equation

HRID 1198449 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][NH:12][C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[S:9]2)=[CH:4][CH:3]=1.[CH:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[CH:20][C:19]=1[S:28]([N:31]1[CH2:38][CH2:37][CH2:36][C@H:32]1[C:33](Cl)=[O:34])(=[O:30])=[O:29].C(OCC)(=O)C>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[CH2:13][N:12]([C:33](=[O:34])[C@@H:32]3[CH2:36][CH2:37][CH2:38][N:31]3[S:28]([C:19]3[CH:20]=[CH:21][C:22]4[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:18]=3)(=[O:30])=[O:29])[C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[S:9]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 130715242-(4-chlorophenyl)-3,4-dihydro2H-1,4-benzothiazineHCID 13576782(S)-N-(2-naphthalenesulfonyl)prolyl chloride

Product 1

HCID 54249707(R)-2-(4-Chlorophenyl)-4-[(S)-N-(2-naphthalene-sulfonyl)prolyl]-3,4-dihydro-2H-1,4-benzothiazineYield 51.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of (±)-2-(4-chlorophenyl)-3,4-dihydro-2H-1,4-benzothiazine (10.01 g, 0.038 mole) in pyridine (150 ml) is added (S)-N-(2-naphthalenesulfonyl)prolyl chloride (18.57 g, 0.057 mole), and the mixture is stirred at room temperature for 4 hours. To the reaction mixture is added ethyl acetate, and the mixture is washed with 5% hydrochloric acid, water, aqueous sodium hydrogen carbonate solution, water and saline in this order, and the ethyl acetate layer is separated, dried over sodium sulfate and distilled to remove the solvent. The resulting caramel is subjected to silica gel column chromatography (hexane:ethyl acetate=5:1-3:1). From the fraction eluted first there is obtained (R)-2-(4-chlorophenyl)-4-[(S)-N-(2-naphthalenesulfonyl)prolyl]-3,4-dihydro 2H-1,4-benzothiazine (10.75 g, 51%) as crystals. M.p. 147°-151° C.

Workup

  1. washthe mixture is washed with 5% hydrochloric acid, water, aqueous sodium hydrogen carbonate solution, water and saline in this order
  2. customthe ethyl acetate layer is separated
  3. dry with materialdried over sodium sulfate
  4. distillationdistilled
  5. customto remove the solvent
  6. washFrom the fraction eluted first there

Sources & evidence

ORD record
ord-a427929280924b28afd13503d52d2f11
Source dataset
uspto-grants-1994_01
Patent number
US05281592

Reaction notes

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