Hydrochloric Acid → (1R,2S,7R,8S)-N-{3-[6-hydroxy-3-(3-methyl-butyl)-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide

HRID 424219Notes

Reaction equation

HRID 424219 reaction equation
C([O:3][C:4]([C@H:6]1[C@@H:11]([N:12]([C:18](=[O:37])[CH2:19][C:20]2[NH:25][C:24]3[CH:26]=[CH:27][C:28]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])=[CH:29][C:23]=3[S:22](=[O:36])(=[O:35])[N:21]=2)[CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C@H:10]2[CH2:38][C@@H:7]1[CH2:8][CH2:9]2)=O)C.[O-]CC.[Na+].Cl>C(O)C>[OH:3][C:4]1[C@H:6]2[C@H:11]([C@H:10]3[CH2:38][C@@H:7]2[CH2:8][CH2:9]3)[N:12]([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C:18](=[O:37])[C:19]=1[C:20]1[NH:25][C:24]2[CH:26]=[CH:27][C:28]([NH:30][S:31]([CH3:34])(=[O:32])=[O:33])=[CH:29][C:23]=2[S:22](=[O:36])(=[O:35])[N:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 66673581(1S,2R,3S,4R)-3-[[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-(3-methyl-butyl)-amino]-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester

Product 1

HCID 135976563(1R,2S,7R,8S)-N-{3-[6-hydroxy-3-(3-methyl-butyl)-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamideYield 56.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

The crude (1S,2R,3S,4R)-3-[[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-(3-methyl-butyl)-amino]-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester was dissolved in ethanol (7 mL) and a 21 wt. % solution of sodium ethoxide in ethanol (1.15 mL, 3.25 mmol) was added into the above solution. The mixture was stirred at 60° C. for 4 h and cooled down to 25° C. The mixture was poured into 0.5 M aqueous hydrochloric acid solution (100 mL). The aqueous layer was extracted with ethyl acetate (2×100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the crude product, which was purified by flash column chromatography (Teledyne Isco RediSep column; 100% ethyl acetate) to afford the desired product, (1R,2S,7R,8S)—N-{3-[6-hydroxy-3-(3-methyl-butyl)-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (0.19 g, 0.364 mmol, 56.1% over two steps), as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ: 0.89-0.93 (6H, m), 1.16-1.23 (2H, m), 1.28-1.32 (1H, m), 1.35-1.62 (7H, m), 1.99-1.99 (1H, m), 2.52-2.54 (1H, m), 2.63 (1H, bs), 3.06 (3H, s), 3.62-3.72 (2H, m), 7.50 (1H, dd, J1=8.9 Hz, J2=2.2 Hz), 7.57-7.59 (2H, m), 10.17 (1H, s). LC-MS (ESI) calcd for C23H30N4O6S2 522.16, found 523.6 [M+H+].

Workup

  1. temperaturecooled down to 25° C
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford the crude product, which
  7. customwas purified by flash column chromatography (Teledyne Isco RediSep column; 100% ethyl acetate)

Sources & evidence

ORD record
ord-44afcface25849c39ecdfe50ba81f23d
Source dataset
uspto-grants-2012_01
Patent number
US08101800B2

Reaction notes

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