Trifluoroacetic acid → HCID 67002159, compound

HRID 2279240Notes

Reaction equation

HRID 2279240 reaction equation
CN(CC)C.[CH:6]1([C:9]([N:11]2[CH2:17][CH2:16][CH:15]3[CH2:18][N:19](C(OC(C)(C)C)=O)[CH2:20][CH2:21][N:14]3[C:13]3[N:29]=[CH:30][CH:31]=[CH:32][C:12]2=3)=O)[CH2:8][CH2:7]1.[OH-].[Na+].FC(F)(F)C(O)=O>O1CCCC1.CO>[CH:6]1([CH2:9][N:11]2[CH2:17][CH2:16][CH:15]3[CH2:18][NH:19][CH2:20][CH2:21][N:14]3[C:13]3[N:29]=[CH:30][CH:31]=[CH:32][C:12]2=3)[CH2:7][CH2:8]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11723DimethylethylamineHCID 14798Sodium HydroxideHCID 67001731HCID 67001731, compound

Product 1

HCID 67002159HCID 67002159, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution alane-N,N-dimethylethylamine (0.5 M in toluene, 2.84 mL, 1.42 mmol) was added under nitrogen to an ice-cooled solution of the product of Example 72B (176 mg, 0.473 mmol) in tetrahydrofuran (8 mL). The reaction was stirred with ice cooling for 15 minutes and then warmed to room temperature and stirred for 30 minutes. Methanol (1 mL) was added followed after 5 minutes by addition of 25% NaOH (1 mL). The mixture was stirred for 10 minutes and then concentrated under vacuum. The residue was taken up with brine (10 mL) and extracted with CH2Cl2 (2×20 mL). The combined organic phases were dried (Na2SO4) and concentrated under vacuum. The residue was dissolved in CH2Cl2 (5 mL) and stirred with ice cooling under nitrogen for 10 minutes. Trifluoroacetic acid (1.0 mL, 13 mmol) was added gradually over 0.5 minute, and the reaction was stirred with ice cooling for 1 hour and then warmed to room temperature for 1 hour. The solution was concentrated under vacuum, and the residue was purified by HPLC (30×100 mm, C18, Waters XBridge™ column eluted with 0.1 M aqueous (NH4)2CO3-methanol, 80:20-0:100 over 15 minutes) to provide the title compound: 1H NMR (300 MHz, CD3OD) δ ppm 0.18-0.27 (m, 2H), 0.51-0.60 (m, 2H), 0.93-1.09 (m, 1H), 1.67-1.80 (m, 1H), 1.80-1.94 (m, 1H), 2.73-2.86 (m, 2H), 2.87-3.04 (m, 4H), 3.11-3.28 (m, 3H), 3.41-3.51 (m, 2H), 6.84 (dd, J=7.8, 5.1 Hz, 1H), 7.12 (dd, J=8.0, 1.5 Hz, 1H), 7.70 (dd, J=5.1, 1.7 Hz, 1H); MS (DCI) m/z 259 (M+H)+.

Workup

  1. stirringstirred for 30 minutes
  2. stirringThe mixture was stirred for 10 minutes
  3. concentrationconcentrated under vacuum
  4. extractionextracted with CH2Cl2 (2×20 mL)
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. concentrationconcentrated under vacuum
  7. dissolutionThe residue was dissolved in CH2Cl2 (5 mL)
  8. stirringstirred with ice cooling under nitrogen for 10 minutes
  9. stirringthe reaction was stirred with ice cooling for 1 hour
  10. temperaturewarmed to room temperature for 1 hour
  11. concentrationThe solution was concentrated under vacuum
  12. customthe residue was purified by HPLC (30×100 mm, C18, Waters XBridge™ column eluted with 0.1 M aqueous (NH4)2CO3-methanol, 80:20-0:100 over 15 minutes)

Sources & evidence

ORD record
ord-bfff1bb447b442a2b662b9f93ee1b49b
Source dataset
uspto-grants-2015_09
Patent number
US09133206B2

Reaction notes

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