Acetic Acid → HCID 131726783, compound

HRID 1466717Notes

Reaction equation

HRID 1466717 reaction equation
O1CCCCC1[O:7][CH:8]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([CH3:43])([CH3:42])[CH2:33][C:34](=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[N:37][CH:36]=1)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([CH3:26])([CH3:25])[CH2:15][O:16][C:17](=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[N:20][CH:19]=1.C(O)(=O)C.C1COCC1>O>[OH:7][CH:8]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([CH3:43])([CH3:42])[CH2:33][C:34](=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[N:37][CH:36]=1)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([CH3:26])([CH3:25])[CH2:15][O:16][C:17](=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[N:20][CH:19]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 131726782HCID 131726782, compound

Product 1

HCID 131726783HCID 131726783, compoundYield 59.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Nicotinic acid 8-(tetrahydropyran-2-yloxy)-2,2,14,14-tetramethyl-15-nicotinoylpentadecyl ester (9.0 g, 14.7 mmol) was heated in a mixture of glacial acetic acid, THF, and water (160 mL/80 mL/40 mL) to 45° C. for 6 h, then stirred overnight at ambient temperature. After the reaction was completed (TLC), the reaction mixture was poured onto ice (220 g), stirred for 30-45 min and extracted with methylene chloride (4×100 mL). The combined organic layers were washed with saturated NaHCO3 solution (4×100 mL) and brine (100 mL), dried over MgSO4, and concentrated to give a crude oil (7.9 g). Purification by chromatography (silica gel, 75 g, heptanes:ethyl acetate=1:1) afforded nicotinic acid 8-hydroxy-2,2,14,14-tetramethyl-15-nicotinoylpentadecyl ester (4.5 g, 58%) as a white solid. Mp 65-67° C. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm): 9.24 (s, 2H), 8.78 (d, J=3.8 Hz, 2H), 8.31 (d, J=8.0 Hz, 2H), 7.42 (dd, J=8.0, 4.9 Hz, 2H), 4.08 (s, 4H), 3.58 (br s, 1H), 2.02 (br s, 1H, OH), 1.62-1.08 (m, 20H), 1.00 (s, 12H). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm): 164.96, 153.03, 150.53, 136.81, 126.17, 123.16, 73.18, 71.58, 39.17, 37.41, 33.96, 30.44, 25.61, 24.37, 23.78. HRMS (EI, nba): Calcd for C31H47N2O5 (MH+): 527.3485. found: 527.3482. HPLC: 99.7% pure. Elemental analysis (C31H46N2O5): Calcd for C, 70.69; H, 8.80; N, 5.32. Found: C, 70.63; H, 8.83; N, 5.41.

Workup

  1. additionthe reaction mixture was poured onto ice (220 g)
  2. stirringstirred for 30-45 min
  3. extractionextracted with methylene chloride (4×100 mL)
  4. washThe combined organic layers were washed with saturated NaHCO3 solution (4×100 mL) and brine (100 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customto give a crude oil (7.9 g)
  8. customPurification by chromatography (silica gel, 75 g, heptanes:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-5cc30d6fd19f4496b41bd0efe825b911
Source dataset
uspto-grants-2015_04
Patent number
US09000041B2

Reaction notes

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