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

HRID 548337Notes

Reaction equation

HRID 548337 reaction equation
C(O[C:4]([C@H:6]1[C@@H:11]([N:12]([C:18](=[O:33])[CH2:19][C:20]2[NH:25][C:24]3[CH:26]=[CH:27][C:28]([I:30])=[CH:29][C:23]=3[S:22](=[O:32])(=[O:31])[N:21]=2)[CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C@H:10]2[CH2:34][C@@H:7]1[CH2:8][CH2:9]2)=[O:5])C.[O-]CC.[Na+].Cl>C(O)C>[OH:5][C:4]1[C@H:6]2[C@H:11]([C@H:10]3[CH2:34][C@@H:7]2[CH2:8][CH2:9]3)[N:12]([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C:18](=[O:33])[C:19]=1[C:20]1[NH:25][C:24]2[CH:26]=[CH:27][C:28]([I:30])=[CH:29][C:23]=2[S:22](=[O:32])(=[O:31])[N:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 66674587(1S,2R,3S,4R)-3-[[2-(7-iodo-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 136402483(1R,2S,7R,8S)-6-hydroxy-5-(7-iodo-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-3-(3-methyl-butyl)-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-oneYield 40.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

The crude (1S,2R,3S,4R)-3-[[2-(7-iodo-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 (0.546 mmol) was dissolved in ethanol (5 mL), and a 21 wt. % solution of sodium ethoxide in ethanol (1 mL, 2.73 mmol) was added into the above solution. The mixture was stirred at 60° C. for 6 h and allowed to cool to 25° C. The mixture was poured into 0.5 M aqueous hydrochloric acid solution (100 mL). The product started to precipitate and was collected by vacuum filtration. The precipitate was purified by flash column chromatography (Teledyne Isco RediSep column; 40% ethyl acetate in hexanes) to afford the desired product, (1R,2S,7R,8S)-6-hydroxy-5-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-3-(3-methyl-butyl)-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (0.122 g, 0.2 mmol, 40.3% over two steps), as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 0.92 (6H, d, J=5.4 Hz), 1.16-1.63 (9H, m), 2.99-3.12 (2H, m), 3.62-3.71 (2H, m), 7.37 (1H, d, J=8.3 Hz), 7.99 (1H, dd, J1=8.6 Hz, J2=1.6 Hz), 8.08 (1H, s). LC-MS (ESI) calcd for C22H26IN3O4S 555.07, found 556.3 [M+H+].

Workup

  1. temperatureto cool to 25° C
  2. customto precipitate
  3. filtrationwas collected by vacuum filtration
  4. customThe precipitate was purified by flash column chromatography (Teledyne Isco RediSep column; 40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3266de0fa69f404885e62671f71b4b09
Source dataset
uspto-grants-2011_05
Patent number
US07939524B2

Reaction notes

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