Sodium ethoxide → 1-[(4-fluorophenyl)methyl]-4-hydroxy-3-(7-iodo-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-3-yl)-4a,5,6,7,8,8a-hexahydroquinolin-2-one

HRID 731365Notes

Reaction equation

HRID 731365 reaction equation
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]1[N:12]([CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)[C:13](=[O:28])[CH2:14][C:15]1[NH:20][C:19]2[CH:21]=[CH:22][C:23]([I:25])=[CH:24][C:18]=2[S:17](=[O:27])(=[O:26])[N:16]=1)=O)C.[O-]CC.[Na+]>C(O)C>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][N:12]2[CH:7]3[CH:6]([CH2:11][CH2:10][CH2:9][CH2:8]3)[C:4]([OH:3])=[C:14]([C:15]3[NH:20][C:19]4[CH:21]=[CH:22][C:23]([I:25])=[CH:24][C:18]=4[S:17](=[O:26])(=[O:27])[N:16]=3)[C:13]2=[O:28])=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 2723922Sodium ethoxideHCID 576712042-{(4-Fluoro-benzyl)-[2-(7-iodo-1,1-dioxo-1,4-dihydro-1lambda6 benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid ethyl ester

Product 1

HCID 1359557921-[(4-fluorophenyl)methyl]-4-hydroxy-3-(7-iodo-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-3-yl)-4a,5,6,7,8,8a-hexahydroquinolin-2-oneYield 12.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of the crude 2-{(4-fluoro-benzyl)-[2-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid ethyl ester in ethanol (20 mL) was treated with a 21% w/w solution of sodium ethoxide in ethanol (9.28 g, 28.64 mmol) and stirred for 16 h at 60° C. Upon cooling, the reaction mixture was then quenched with 1.0 M aqueous hydrochloric acid solution (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered, and dried in vacuo. The residue was purified by flash column chromatography (Teledyne Isco RediSep Column; 0-50% ethyl acetate in hexanes) to afford the desired product, 1-(4-fluoro-benzyl)-4-hydroxy-3-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-4a,5,6,7,8,8a-hexahydro-1H-quinolin-2-one (516 mg, 0.888 mmol, 12.4% over two steps), as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.07-1.81 (8H, m), 2.21-2.34 (1H, m), 3.50-5.03 (3H, m), 7.11-8.03 (7H, m). LC-MS (ESI) calcd for C23H21FIN3O4S 581.03, found 582.1 [M+H+].

Workup

  1. temperatureUpon cooling
  2. customthe reaction mixture was then quenched with 1.0 M aqueous hydrochloric acid solution (20 mL)
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customdried in vacuo
  8. customThe residue was purified by flash column chromatography (Teledyne Isco RediSep Column; 0-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bd4ce126606c4bbf8d7043e9608da77c
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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