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

HRID 851914노트

반응식

HRID 851914 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매4회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-d813652ea3d7497a8924bd166a7ccb7d
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07253164B2

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