Methanol → Methyl 6-(adamantan-1-ylmethoxy)-5-chloronicotinate

HRID 1849579Notes

Reaction equation

HRID 1849579 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:21]([Cl:22])=[CH:20][C:16]([C:17]([OH:19])=[O:18])=[CH:15][N:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH3:23]N(C)CCCN=C=NCC.C(N(CC)CC)C.CO>C(Cl)Cl>[C:1]12([CH2:11][O:12][C:13]3[C:21]([Cl:22])=[CH:20][C:16]([C:17]([O:19][CH3:23])=[O:18])=[CH:15][N:14]=3)[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2

Participants

6

Procedure

A solution of 6-(adamantan-1-ylmethoxy)-5-chloronicotinic acid (4.20 g, 13.10 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (5.00 g, 26.10 mmol), triethylamine (3.6 mL, 26.10 mmol) and methanol (1.05 mL, 26.10 mmol) in methylene chloride (100 mL) was stirred under nitrogen for 18 h. The reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (300 mL). The mixture was washed with a 1:1(v/v) mixture of 1 M aqueous hydrochloric acid/brine (2×100 mL), brine (2×100 mL); dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was purified by flash chromatography eluting with 10% ethyl acetate in hexanes to afford the title compound as a white solid (1.90 g, 43%); 1H NMR (300 MHz, CDCl3) δ 8.66-8.62 (m, 1H), 8.19-8.16 (m, 1H), 3.99 (s, 2H), 3.89 (s, 3H), 2.04-1.96 (m, 3H), 1.78-1.62 (m, 12H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate (300 mL)
  3. washThe mixture was washed with a 1:1(v/v)
  4. additionmixture of 1 M aqueous hydrochloric acid/brine (2×100 mL), brine (2×100 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography
  9. washeluting with 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6dfd034038e049f9b6c935578efa70ec
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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