Triethylamine → HCID 56971146, compound

HRID 1526430Notes

Reaction equation

HRID 1526430 reaction equation
[S:1]1[C:9]2[CH2:8][CH2:7][NH:6][CH2:5][C:4]=2[CH:3]=[CH:2]1.[CH2:10]([O:12][C:13](=[O:28])[C:14]([CH3:27])([CH3:26])[CH2:15][CH2:16][CH:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[Cl:24])[CH3:11].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C1COCC1.CN(C1C=CN=CC=1)C>[CH2:10]([O:12][C:13](=[O:28])[C:14]([CH3:27])([CH3:26])[CH2:15][CH2:16][CH:17]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[Cl:24])[N:6]1[CH2:7][CH2:8][C:9]2[S:1][CH:2]=[CH:3][C:4]=2[CH2:5]1)[CH3:11]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 30850764,5,6,7-Tetrahydrothieno(3,2-c)pyridineHCID 67512907HCID 67512907, compound

Product 1

HCID 56971146HCID 56971146, compoundYield 67.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

4,5,6,7-Tetrahydrothieno[3,2-c]pyridine (0.65 g, 4.61 mmol) and 5-bromo-5-(2-chlorophenyl)-2,2-dimethylpentanoic acid ethyl ester (1.42 g, 4.08 mmol) were dissolved in THF (5 mL) and triethylamine (3 mL) with a few crystals of DMAP. The solution was heated overnight to 85° C. using an oil bath. After 20 hours, the solution was cooled to room temperature and sodium bicarbonate solution (20 mL) was added. After mixing, the product was extracted with dichloromethane (2×25 mL). The combined dichloromethane fractions were dried over sodium sulfate, filtered, and concentrated. The remaining yellow oil was purified by MPLC on a Companion Chromatography station using silica gel (40 g), eluting with a gradient of 100% heptane to 10% ethyl acetate over 20 minutes followed by a second gradient to 100% ethyl acetate at 40 minutes. The second broad fraction was collected and concentrated to produce 5-(2-chlorophenyl)-5-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,2-dimethylpentanoic acid ethyl ester (Compound Ib, 1.11 g, 67.2% yield) as a light, yellow oil. 1H NMR (300 MHz, CDCl3/TMS): δ=7.46 (dd, 1H, J=7.80, 1.5 Hz), 7.38 (dd, 1H, J=7.80, 1.5 Hz), 7.30-7.15 (m, 2H), 7.04 (d, 1H, J=5.1 Hz), 6.70 (d, 1H, J=5.1 Hz), 4.18 (dd, 1H, J=8.7, 4.5 Hz), 4.08 (q, 2H, J=7.2 Hz), 3.79 (d, 1H, J=14.4 Hz), 3.45 (d, 1H, J=14.4 Hz), 2.90-2.62 (m, 4H), 2.0-1.85 (m, 1H), 1.82-1.68 (m, 1H), 1.49 (dt, 1H, J=13.5, 4.2 Hz), 1.30 (dt, 1H, J=13.5, 4.5 Hz), 1.20 (t, 3H, J=7.2 Hz), 1.10 (s, 6H). 13C NMR (75 MHz, CDCl3/TMS): δ=177.59, 138.99, 134.95, 134.25, 133.59, 129.64, 129.11, 128.07, 126.73, 125.43, 122.61, 63.81, 60.38, 50.63, 47.95, 42.22, 36.43, 28.22, 26.17, 25.52, 25.38, 14.47. MS (MMI-TOF): Calculated for C22H28NO2ClS (MH+): 406.1602. found 406.1576.

Workup

  1. temperatureThe solution was heated overnight to 85° C.
  2. additionAfter mixing
  3. extractionthe product was extracted with dichloromethane (2×25 mL)
  4. dry with materialThe combined dichloromethane fractions were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe remaining yellow oil was purified by MPLC on a Companion Chromatography station
  8. washeluting with a gradient of 100% heptane to 10% ethyl acetate over 20 minutes
  9. waitfollowed by a second gradient to 100% ethyl acetate at 40 minutes
  10. customThe second broad fraction was collected
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-6fab8f2c62144470b573a764ffadccdf
Source dataset
uspto-grants-2015_07
Patent number
US09085585B2

Reaction notes

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