Hydrochloric Acid → ethyl 2-(3,4-dihydro-4-(carboxymetyl)-3-oxo-2H-benzo[b][1,4]thiazin-2-yl)acetate

HRID 2105529Notes

Reaction equation

HRID 2105529 reaction equation
[Li+].CC([N-]C(C)C)C.[CH2:9]([O:11][C:12](=[O:25])[CH2:13][CH:14]1[C:19](=[O:20])[NH:18][C:17]2[CH:21]=[CH:22][CH:23]=[CH:24][C:16]=2[S:15]1)[CH3:10].Br[CH2:27][C:28]([OH:30])=[O:29].Cl>C1COCC1.C(OCC)C>[C:28]([CH2:27][N:18]1[C:19](=[O:20])[CH:14]([CH2:13][C:12]([O:11][CH2:9][CH3:10])=[O:25])[S:15][C:16]2[CH:24]=[CH:23][CH:22]=[CH:21][C:17]1=2)([OH:30])=[O:29]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6227Bromoacetic AcidHCID 2724682Lithium diisopropylamideHCID 2778792Ethyl 2-(3-oxo-3,4-dihydro-2h-1,4-benzothiazin-2-yl)acetate

Product 1

HCID 22736612ethyl 2-(3,4-dihydro-4-(carboxymetyl)-3-oxo-2H-benzo[b][1,4]thiazin-2-yl)acetateYield 50%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent4×

Procedure

To a solution of LDA (2M) in THF (3.26 mmol) in 2 mL of anhydrous THF at 0° C. and under nitrogen, a solution of (3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-2-yl)-acetic acid ethyl ester (1.62 mmol) in 4 mL of dry THF is added dropwise. The temperature of the reaction mixture is held at room temperature for 2 hours and then dropped to −78° C. A solution of 2-bromo acetic acid (1.64 mmol) in 2 mL of anhydrous THF is added and the temperature of the reaction is slowly let to rise to room temperature. HCl (1M) is added to reach pH=1. Ethyl ether is added and the phases are separated. The organic phase is dried on Na2SO4, the drying agent is filtered and the solvent evaporated. The crude product is purified by automated column chromatography (hexane/EtOAc) to give the product ethyl 2-(3,4-dihydro-4-(carboxymetyl)-3-oxo-2H-benzo[b][1,4]thiazin-2-yl)acetate. Yield: 50%. 1H NMR (400 MHz, CDCl3): δ 9.07 (bs, 1H), 7.38 (d, J=7.6 Hz, 1H), 7.27 (t, J=7.6 Hz, 1H), 7.07 (t, J=7.6 Hz, 1H), 6.93 (d, J=7.6 Hz, 1H), 4.69 (dd, 2H), 4.18 (dd, 2H), 3.99 (t, J=6.4 Hz, 1H), 3.04 (dd, J1=6.4 Hz, J2=16.8 Hz, 1H), 2.58 (dd, 1H), 1.26 (m, 3H).

Workup

  1. additiondropped to −78° C
  2. customto rise to room temperature
  3. customthe phases are separated
  4. customThe organic phase is dried on Na2SO4
  5. filtrationthe drying agent is filtered
  6. customthe solvent evaporated
  7. customThe crude product is purified by automated column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-a4f396d52c294728b8cd4f8cfef2b1b5
Source dataset
uspto-grants-2009_08
Patent number
US07579363B2

Reaction notes

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