Trifluoroacetic acid → 7-(2-Chlorophenyl)-2,2 dimethyl-7-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-heptanoic acid ethyl ester

HRID 1801549Notes

Reaction equation

HRID 1801549 reaction equation
C(OC([N:8]1[C:16]2[CH2:15][CH2:14][N:13]([CH:17]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[Cl:36])[CH2:18][CH2:19][CH2:20][CH2:21][C:22]([C:25]([O:27][CH2:28][CH3:29])=[O:26])([CH3:24])[CH3:23])[CH2:12][C:11]=2[CH:10]=[CH:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH2:28]([O:27][C:25](=[O:26])[C:22]([CH3:24])([CH3:23])[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[Cl:36])[N:13]1[CH2:14][CH2:15][C:16]2[NH:8][CH:9]=[CH:10][C:11]=2[CH2:12]1)[CH3:29]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 675180355-[1-(2-Chlorophenyl)-6-ethoxycarbonyl-6-methylheptyl]-4,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester

Product 1

HCID 569713857-(2-Chlorophenyl)-2,2 dimethyl-7-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-heptanoic acid ethyl esterYield 41.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

5-[1-(2-Chlorophenyl)-6-ethoxycarbonyl-6-methylheptyl]-4,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (1.0 g, 1.94 mmol) was dissolved in dichloromethane (40 mL) under an argon atmosphere. Trifluoracetic acid (4.0 mL, 40.7 mmol) was added to the solution. After 2 hours, the mixture was poured into ice/water (90 mL) and extracted with dichloromethane (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, ethyl acetate/heptane=1/9 to 1/3) to afford 7-(2-chlorophenyl)-2,2 dimethyl-7-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-heptanoic acid ethyl ester (Compound Il, 330 mg, 41.2% yield) as a yellow oil. 1H NMR (Field: 300 MHz, Solvent: CDCl3/TMS) δ (ppm): 7.93 (br, 1H), 7.53 (d, 1H, J=7.5 Hz), 7.35 (d, 1H, J=7.8 Hz), 7.26-7.13 (m, 2H), 6.58 (s, 1H), 5.93 (s, 1H), 4.16 (dd, 1H, J=9.3, 3.9 Hz), 4.10 (q, 2H, J=7.2 Hz), 3.75 (d, 1H, J=13.5 Hz), 3.39 (d, 1H, J=13.2 Hz), 2.80-2.56 (m, 4H), 2.04-1.78 (m, 2H), 1.44-1.39 (m, 2H), 1.21 (t, 3H, J=6.9 Hz), 1.26-1.16 (m, 4H), 1.11 (s, 6H). 13C NMR (Field: 75 MHz, Solvent: CDCl3/TMS) δ (ppm): 178.01, 139.87, 134.94, 129.40, 129.22, 127.86, 126.81, 125.01, 116.45, 115.70, 105.69, 63.80, 60.37, 48.78, 48.29, 42.31, 40.81, 33.29, 26.15, 25.36, 23.95, 14.52. HRMS (DART-TOF): Calculated for C24H33ClN2O2 (M+H)+: 717.2303, 417.2295 found.

Workup

  1. extractionextracted with dichloromethane (3×20 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by column chromatography (silica gel, ethyl acetate/heptane=1/9 to 1/3)

Sources & evidence

ORD record
ord-b80f8c47f0214c7994603a99fea063ee
Source dataset
uspto-grants-2013_01
Patent number
US08349833B2

Reaction notes

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