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HRID731327

反应详情

EQUATION

反应方程式

HRID 731327 的结构方程式

REACTANTS

反应物

2
结构：CC[O-].[Na+]
HCID2723922

Ethanol, sodium salt

C2H5NaO

结构：COC(=O)[C@H]1CCCC[C@H]1N(Cc1ccc(F)cc1)C(=O)CC1=NS(=O)(=O)c2cc(NS(C)(=O)=O)ccc2N1
HCID57671179

未命名化合物

PRODUCTS

生成物

1
结构：CS(=O)(=O)Nc1ccc2c(c1)S(=O)(=O)N=C(C1=C(O)[C@H]3CCCC[C@H]3N(Cc3ccc(F)cc3)C1=O)N2
HCID135955692

未命名化合物

收率 40%

AUXILIARIES

试剂、催化剂与溶剂

1
结构：CCO
溶剂HCID702

Ethanol

C2H6O

2 次

CONDITIONS

反应条件

温度
60 °C

PROCEDURE

实验过程

The crude (1S,2R)-2-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid methyl ester (4.97 mmol) was dissolved in ethanol (50 mL) at 25° C. and a 21% w/w solution of sodium ethoxide in ethanol (2.86 mL) was added. The reaction mixture was heated to 60° C. for 8 h, then was cooled to 25° C. and partitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate, decanted, and were concentrated in vacuo. The residue was purified by flash column chromatography (Teledyne Isco RediSep Flash Column 150 g; 0-6% methanol in dichloromethane) to afford the desired product, (4aS,8aR)-N-{3-[1-(4-fluoro-benzyl)-4-hydroxy-2-oxo-1,2,4a,5,6,7,8,8a-octahydro-quinolin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (0.96 g, 1.75 mmol, 40% over 4 steps), as a pale yellow foam. 1H NMR (400 MHz, DMSO-d6) δ: 1.10-1.26 (3H, m), 1.36-1.48 (3H, m), 1.61-1.64 (1H, m), 1.77-1.80 (1H, m), 2.27-2.31 (1H, m), 3.06 (3H, s), 3.59 (1H, bs), 4.32 (1H, bs), 4.45 (1H, s), 4.99 (1H, d, J=15.3 Hz), 7.07-7.11 (1H, m), 7.12-7.17 (2H, m), 7.29-7.33 (1H, m), 7.39-7.42 (1H, m), 7.51 (1H, dd, J1=2.3 Hz, J2=8.5 Hz), 7.57 (1H, s), 7.58-7.59 (1H, m), 10.17 (1H, s), 13.80 (1H, s). LC-MS (ESI) calcd for C24H25FN4O6S2 548.12, found 549.4 [M+H+]. >99.5% e.e. as determined by chiral HPLC analysis: column: Chiralpak AS-RH 4.6×250 mm ID 5 um, solvent: acetonitrile+0.05% trifluoroacetic acid (mobile phase B); water+0.05% trifluoroacetic acid (mobile phase A), gradient: 50% to 90% mobile phase B over 15 min.

WORKUP

后处理

  1. temperaturewas cooled to 25° C.
  2. custompartitioned between 1.0 M aqueous hydrochloric acid solution (150 mL) and ethyl acetate (2×150 mL)
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. customdecanted
  5. concentrationwere concentrated in vacuo
  6. customThe residue was purified by flash column chromatography (Teledyne Isco RediSep Flash Column 150 g; 0-6% methanol in dichloromethane)