Trifluoroacetic acid → HCID 67481463, compound

HRID 869037Notes

Reaction equation

HRID 869037 reaction equation
[C:1](O)([C:3](F)(F)F)=O.[CH3:8][C:9]1([CH3:29])[C:13]([CH3:15])([CH3:14])[O:12][B:11]([C:16]2[CH2:17][CH2:18][N:19]([C:22](OC(C)(C)C)=[O:23])[CH2:20][CH:21]=2)[O:10]1.CCN(CC)CC.C(Cl)(=O)CC>C(Cl)Cl>[CH3:8][C:9]1([CH3:29])[C:13]([CH3:14])([CH3:15])[O:12][B:11]([C:16]2[CH2:17][CH2:18][N:19]([C:22](=[O:23])[CH2:1][CH3:3])[CH2:20][CH:21]=2)[O:10]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 62324Propionyl chlorideHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 67481463HCID 67481463, compoundYield 90.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

TFA (14.75 g, 9.966 mL, 129.4 mmol) was added to a stirred solution of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (5000 mg, 16.17 mmol) in DCM (40 mL) at 0° C. and the reaction stirred at this temperature for 1.5 hours. The solvent was removed in vacuo and the residue azeotroped with MeCN (×3). The residue was re-dissolved in DCM (50 mL) and cooled to 0° C. Et3N (6.545 g, 9.015 mL, 64.68 mmol) was added followed by a solution of propionyl chloride (1.646 g, 1.546 mL, 17.79 mmol) in DCM (5 mL). The reaction mixture was allowed to warm to ambient temperature over 1 hour. The mixture was diluted with DCM and washed with 1:1 1M HCl/brine (×2), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 120 g column, eluting with 20 to 80% EtOAc/Petroleum Ether) to give the sub-title product as a white solid (3.87 g, 90% Yield). 1H NMR (400.0 MHz, CDCl3) δ 1.15 (t, 3H), 1.27 (s, 12H), 2.20-2.44 (m, 4H), 3.47 (t, 1H), 3.64 (s, 1H), 4.06 (d, 2H) and 6.48 (d, 1H) ppm; MS (ES+) 266.3.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue azeotroped with MeCN (×3)
  3. dissolutionThe residue was re-dissolved in DCM (50 mL)
  4. temperatureto warm to ambient temperature over 1 hour
  5. washwashed with 1:1 1M HCl/brine (×2)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (ISCO Companion™, 120 g column, eluting with 20 to 80% EtOAc/Petroleum Ether)

Sources & evidence

ORD record
ord-d7a5aec7e4d7405abf13d47f7e1ff3c1
Source dataset
uspto-grants-2015_03
Patent number
US08969356B2

Reaction notes

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