Trifluoroacetic acid → 1,1'-[(Propane-1,3-diyl)dioxy]bis[(11aS)-8-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5-one]

HRID 227168Notes

Reaction equation

HRID 227168 reaction equation
C(O)(C(F)(F)F)=O.[CH2:8]([O:43][CH:44]1[C@H:48]2[C@H:49](OC3CCCCO3)[N:50](C(OC(C)(C)C)=O)[C:51]3[CH:58]=[C:57]([O:59][CH3:60])[CH:56]=[CH:55][C:52]=3[C:53](=[O:54])[N:47]2[CH2:46][CH2:45]1)[CH2:9][CH2:10][O:11][CH:12]1[C@H:16]2[C@H:17](OC3CCCCO3)[N:18](C(OC(C)(C)C)=O)[C:19]3[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:20]=3[C:21](=[O:22])[N:15]2[CH2:14][CH2:13]1.C([O-])(O)=O.[Na+]>CO.C(Cl)(Cl)Cl>[CH2:8]([O:43][CH:44]1[C@@H:48]2[CH:49]=[N:50][C:51]3[CH:58]=[C:57]([O:59][CH3:60])[CH:56]=[CH:55][C:52]=3[C:53](=[O:54])[N:47]2[CH2:46][CH2:45]1)[CH2:9][CH2:10][O:11][CH:12]1[C@@H:16]2[CH:17]=[N:18][C:19]3[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:20]=3[C:21](=[O:22])[N:15]2[CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86760913HCID 86760913, compound

Product 1

HCID 669161781,1'-[(Propane-1,3-diyl)dioxy]bis[(11aS)-8-methoxy-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5-one]Yield 75%

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Procedure

95% TFA (3 mL) was added drop-wise to dimer compound 8a (80 mg, 0.08 mmol) at 0° C. This was then stirred for 1 hr and the mixture was poured into saturated NaHCO3 (30 mL) solution to naturalize the reaction mixture. The mixture was extracted with chloroform (3×20 mL). The organic layer was then washed water (20 mL), brine (20 mL) then dried (MgSO4) and filtrated. The excess solvent was removed under reduced pressure to give the crude product, which was subjected to flash column chromatography (SiO2, 2% methanol-chloroform). Removal of excess eluent under reduced pressure without heating afforded the final product 9a (31 mg, 0.06 mmol, 75%) as a solid: [α]20D=+515° (c=0.10, CHCl3);—1H NMR (CDCl3, 400 MHz): δ 2.01-2.11 (m, 4H, 2-H, 2′-H), 2.28-2.36 (m, 4H, 1-H, 1′-H), 2.38-2.45 (m, 2H, 13-H), 3.52-3.61 (m, 2H, 3-H, 3′-H), 3.67-3.75 (m, 2H, 11a-H, 11a′-H), 3.77-3.85 (m, 2H, 3-H, 3′-H), 3.90 (s, 6H, 7-OMe, 7′-OMe), 4.23-4.30 (m, 4H, 12-H, 12′-H), 6.79 (s, 2H, 9-H, 9′-H), 7.53 (s, 2H, 6-H, 6′-H), 7.65 (d, 2H, J=4, 11-H, 11′-H); 13C NMR (CDCl3, 400 MHz): δ 24.1, 29.0, 29.6, 46.6, 53.7, 56.0, 65.6, 109.6, 112.9, 120.2, 140.7, 146.9, 151.8, 162.3, 164.6; IR (neat): 3350, 2956, 1599, 1506, 1447, 1385, 1262, 1216, 1091 cm−1; MS (FAB) m/z (relative intensity) 597 ([M+2×MeOH]+., 22), 565 ([M+MeOH]+., 25), 533 (M+., 100).

Workup

  1. extractionThe mixture was extracted with chloroform (3×20 mL)
  2. dry with materialwashed water (20 mL), brine (20 mL) then dried (MgSO4)
  3. filtrationfiltrated
  4. customThe excess solvent was removed under reduced pressure
  5. customto give the crude product, which
  6. customRemoval of excess eluent under reduced pressure
  7. temperaturewithout heating

Sources & evidence

ORD record
ord-eeb015b0e95e44eb866d81f59f11465f
Source dataset
uspto-grants-2009_07
Patent number
US07557099B2

Reaction notes

Loading…