Ammonium formate → cis-4-Amino-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

HRID 427717Notes

Reaction equation

HRID 427717 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([C:16]([F:19])([F:18])[F:17])=[CH:13][CH:14]=2)[C@H:9]([NH:20]C(OCC2C=CC=CC=2)=O)[CH2:8][C@@H:7]1[CH2:31][CH3:32])=[O:5])[CH3:2].C([O-])=O.[NH4+]>[Pd].CO>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([C:16]([F:17])([F:18])[F:19])=[CH:13][CH:14]=2)[C@H:9]([NH2:20])[CH2:8][C@@H:7]1[CH2:31][CH3:32])=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 69578494cis-4-benzyloxycarbonylamino-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

Product 1

HCID 69580533cis-4-Amino-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

A one liter, four neck flask under nitrogen atmosphere was charged with cis4-benzyioxycarbonylamino-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (40.1 g, 89 mmol, 1.0 equiv), methanol (400 mL), and ammonium formate (14.0 g, 223 mmol, 2.5 equiv). 10% Pd/C, 50% waterwet (4.0 g) was added, and the slurry heated to 40° C. over 1 h. After 1.5 h, the mixture was cooled to room temperature and filtered through celite. The cake was washed 2×100 mL methanol. The filtrate was concentrated to approximately 75 mL, transferred to a separatory funnel, and diluted with 400 mL ethyl acetate. The mixture was washed 1×125 mL saturated aq. NaHCO3, 1×100 mL brine, and dried (Na2SO4). The mixture was filtered and the filtrate concentrated to a clear oil. The oil was crystallized from 100 mL n-heptane to give cis-4-amino-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester as a white crystalline solid (26.05 g, 93%): mp 61.5-63.50° C.; 1H NMR (CDCl3, 400 MHz) δ0.79 (t, 3H, J=7.5 Hz), 1.24 (m, 4H), 1.42 (m, 1H), 1.51 (br s, 2H), 1.62 (m, 1H), 2.46 (m, 1H), 3.73 (m, 1H) , 4.17 (m, 2H), 4.36 (m, 1H), 7.44 (m, 2H), 7.66 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ154.6, 139.3, 138.9, 126.3 (q, J=32 Hz), 125.7, 124.3 (q, J=271 Hz), 123.5, 119.8, 61.96, 54.16, 46.91, 41.50, 28.85, 14.38, 9.60; DEPT spectrum: quaternary carbons δ154.6, 139.3, 138.9, 126.3, 124.3; CH carbons δ125.7, 123.5, 119.8, 54.16, 46.91; CH2 carbons δ61.96, 41.50, 28.85; CH3 carbons δ14.38, 9.60; IR (drifts) 3350 (s), 3293 (m), 2972 (s), 1697 (vs); MS (ES+) m/z (rel. intensity) 358 (M+H+CH3CN+, 55), 317 (M+H+, 7), 300 (100); Anal. Calcd for C15H19N2O2F3: C, 56.96; H, 6.06; N, 8.86. Found: C, 56.86; H, 6.28; N, 8.82.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. filtrationfiltered through celite
  3. washThe cake was washed 2×100 mL methanol
  4. concentrationThe filtrate was concentrated to approximately 75 mL
  5. customtransferred to a separatory funnel
  6. additiondiluted with 400 mL ethyl acetate
  7. washThe mixture was washed 1×125 mL saturated aq. NaHCO3, 1×100 mL brine
  8. dry with materialdried (Na2SO4)
  9. filtrationThe mixture was filtered
  10. concentrationthe filtrate concentrated to a clear oil
  11. customThe oil was crystallized from 100 mL n-heptane

Sources & evidence

ORD record
ord-31b95174225c472483fbe323594b2616
Source dataset
uspto-grants-2001_11
Patent number
US06313142B1

Reaction notes

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