Ethyl bromopyruvate → 2,2-Dimethyl-3,4-dihydro-2H-[1,4]thiazine-3,5-dicarboxylic acid

HRID 2183572Notes

Reaction equation

HRID 2183572 reaction equation
[NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[C:3]([SH:6])([CH3:5])[CH3:4].Br[CH2:11][C:12](=O)[C:13]([O:15]CC)=[O:14].C(=O)(O)[O-].[Na+]>O.C(#N)C>[CH3:4][C:3]1([CH3:5])[CH:2]([C:7]([OH:9])=[O:8])[NH:1][C:12]([C:13]([OH:15])=[O:14])=[CH:11][S:6]1

Participants

6

Reactant 3

HCID 66144Ethyl bromopyruvateHCID 92863L-PenicillamineHCID 516892Sodium Bicarbonate

Product 1

HCID 223810512,2-Dimethyl-3,4-dihydro-2H-[1,4]thiazine-3,5-dicarboxylic acidYield 34.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of L-penicillamine (298 mg, 2.0 mmol) in water (5 mL) and acetonitrile (5 mL) was added ethyl 3-bromopyruvate (0.25 mL, 390 mg, 2.0 mmol) slowly. To the resulted mixture was added sodium bicarbonate aqueous solution till the pH about 5. Acetonitrile was removed under vacuum and some more water was added. The solution was extracted with methylene chloride. The water phase was separated and freeze-dried under high vacuum. The residue was chromatographed (silica gel, methylene chloride-methanol-acetic acid 100:5:0.3 to 100:10:0.3) to give 150 mg of product (yield 31%). 1HNMR (300 Hz, D3COD) δ (ppm) 6.17 (s, 1H), 4.23 (q, J=7.1 Hz, 2H), 3.79 (s, 1H), 1.48 (s, 3H), 1.31 (t, J=7.1 Hz, 3H), 1.29 (s, 3H). 13CNMR (75 Hz, D3COD) δ (ppm) 173.8, 164.0, 128.0, 102.4, 64.1, 62.2, 41.2, 28.3, 25.2, 14.7 ppm. MS (ESI) m/z 268 (M+Na, 100), 246 (M+1, 5).

Workup

  1. customAcetonitrile was removed under vacuum
  2. additionsome more water was added
  3. extractionThe solution was extracted with methylene chloride
  4. customThe water phase was separated
  5. customfreeze-dried under high vacuum
  6. customThe residue was chromatographed (silica gel, methylene chloride-methanol-acetic acid 100:5:0.3 to 100:10:0.3)

Sources & evidence

ORD record
ord-3495eeb3f4e34f008cdecdba43e73315
Source dataset
uspto-grants-2005_05
Patent number
US06900218B2

Reaction notes

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