Trifluoroacetic acid → (RS) 7-(Methylthio)-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Fumarate

HRID 857467Notes

Reaction equation

HRID 857467 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:29][CH2:28][N:18]2[C:19]3[CH:20]=[C:21]([S:26][CH3:27])[CH:22]=[CH:23][C:24]=3[CH2:25][CH:17]2[CH2:16]1)=O)(C)(C)C.C(=O)([O-])O.[Na+].[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39]>ClCCl.CC(O)C>[C:35]([OH:42])(=[O:41])/[CH:36]=[CH:37]/[C:38]([OH:40])=[O:39].[CH3:27][S:26][C:21]1[CH:22]=[CH:23][C:24]2[CH2:25][CH:17]3[CH2:16][NH:15][CH2:29][CH2:28][N:18]3[C:19]=2[CH:20]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 444972Fumaric AcidHCID 516892Sodium BicarbonateHCID 218687642-Tert-butoxycarbonyl-7-(methylthio)-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole

Product 1

HCID 21868744(RS) 7-(Methylthio)-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole FumarateYield 54%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1 mL) was added to a stirred solution of 2-tert-butoxycarbonyl-7-(methylthio)-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole (70 mg, 0.21 mmol) in dichloromethane. (5 mL) at room temperature under Ar. The reaction was stirred at room temperature for 1 h then poured into saturated aqueous sodium hydrogen carbonate solution (50 mL) and extracted with dichloromethane (3×30 mL). The combined organic extracts, were washed with brine (1×30 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude oil. The oil was dissolved in 2-propanol (5 mL) and heated to reflux. Fumaric acid (1 eq) was added and the solution was cooled to room temperature. The emerging precipitate was filtered, washed with ether and dried to give the product as a white solid (40 mg, 54%). mp 196–198° C. Found: C, 56.50; H, 5.89; N, 8.15%. C12H16N2S. 1.1 C4H4O4 requires: C, 56.60; H, 5.91; N, 8.05%. IR νmax (Nujol)/cm−1 3595, 3188, 2925, 2854, 2457, 1696, 1585, 1485, 1486, 1461, 1402, 1377, 1345, 1317, 1279, 1230, 1179, 1154, 1129, 1066, 1058, 1005, 996, 972, 919, 987, 868, 835, 797, 722, 644, 606, 547 and 482: NMR δH (400 MHz; DMSO-d6) 6.99 (1H, d, J 7.5 Hz), 6.52 (2H, s), 6.47–6.51 (2H, m), 3.69–3.72 (1H, m), 3.50–3.62 (2H, m), 3.05–3.20 (3H, m), 2.91–3.02 (2H, m), 2.65–2.80 (2H, m), 2.43 (3H, s).

Workup

  1. customat room temperature
  2. extractionextracted with dichloromethane (3×30 mL)
  3. washThe combined organic extracts, were washed with brine (1×30 mL)
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. customthe solvent removed under vacuum
  7. customto leave a crude oil
  8. temperatureheated to reflux
  9. temperaturethe solution was cooled to room temperature
  10. filtrationThe emerging precipitate was filtered
  11. washwashed with ether
  12. customdried

Sources & evidence

ORD record
ord-cc508cc762f04b948c30cd2018c7a3fe
Source dataset
uspto-grants-2006_12
Patent number
US07145009B2

Reaction notes

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