Hydrochloric Acid → HCID 178515396, compound

HRID 548331Notes

Reaction equation

HRID 548331 reaction equation
C(O[C:4]([C@H:6]1[C@@H:11]([N:12]([C:21](=[O:35])[CH2:22][C:23]2[NH:28][C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[S:25](=[O:34])(=[O:33])[N:24]=2)[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C@H:10]2[CH2:36][C@@H:7]1[CH2:8][CH2:9]2)=[O:5])C.[O-]CC.[Na+].Cl>C(O)C>[O:34]=[S:25]1(=[O:33])[C:26]2[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=2[N:28]=[C:23]([C:22]2[C:21](=[O:35])[N:12]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[C@@H:11]3[C@H:6]([C:4]=2[OH:5])[C@@H:7]2[CH2:36][C@H:10]3[CH2:9][CH2:8]2)[NH:24]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 66673836HCID 66673836, compound

Product 1

HCID 178515396HCID 178515396, compoundYield 62.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

The crude (1S,2R,3S,4R)-3-[[2-(1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-(4-fluoro-benzyl)-amino]-bicyclo[2.2.1]heptane-2-carboxylic acid ethyl ester was dissolved in ethanol (8 mL), and a 21 wt. % solution of sodium ethoxide in ethanol (1.6 mL, 4.2 mmol) was added into the above solution. The mixture was stirred at 60° C. for 4 h and allowed to cool down 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; 100% ethyl acetate) to afford the desired product, (1R,2S,7R,8S)-5-(1,1-dioxo-1,2-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (0.242 g, 0.517 mmol, 62.1% over two steps), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.16-1.22 (2H, m), 1.40-1.60 (4H, m), 2.51 (1H, bs), 2.64 (1H, d, J=2.1 Hz), 3.03 (1H, d, J=8.0 Hz), 3.54 (1H, d, J=9.3 Hz), 4.42 (1H, d, J=15.6 Hz), 4.97 (1H, d, J=15.7 Hz), 7.15 (2H, t, J=8.8 Hz), 7.33 (2H, dd, J1=8.0 Hz, J2=5.9 Hz), 7.45-7.53 (2H, m), 7.67-7.71 (1H, m), 7.85 (1H, d, J=7.9 Hz). LC-MS (ESI) calcd for C24H22FN3O4S 467.13, found 468.2 [M+H+]. Anal. calcd for C24H22FN3O4S: C, 61.66; H, 4.74; N, 8.99; found C, 61.96; H, 4.88; N, 8.99.

Workup

  1. temperatureto cool down 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; 100% ethyl acetate)

Sources & evidence

ORD record
ord-c09e3dd53994439baa84daa12020d446
Source dataset
uspto-grants-2011_05
Patent number
US07939524B2

Reaction notes

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