3-Hydroxypyridine → HCID 54043018, compound

HRID 617302Notes

Reaction equation

HRID 617302 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[OH:32][CH2:33][C@H:34]1[NH:38][C:37](=[O:39])[CH2:36][CH2:35]1.O[C:41]1[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=1>C1COCC1>[O:39]=[C:37]1[NH:38][C@H:34]([CH2:33][O:32][C:41]2[CH:42]=[N:43][CH:44]=[CH:45][CH:46]=2)[CH2:35][CH2:36]1

Participants

6

Reactant 4

HCID 79713-HydroxypyridineHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 643511(S)-5-(Hydroxymethyl)-2-pyrrolidinone

Product 1

HCID 54043018HCID 54043018, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of triphenylphosphine (52.46 g, 0.20 mol) in 400 mL of anhydrous THF at 0° C. was added diethyl azodicarboxylate (31.49 mL, 0.20 mol) dropwise. The mixture was stirred at 0° C. for 30 minutes, then brought to room temperature. (S)-5-(Hydroxymethyl)-2-pyrrolidinone (Aldrich Chemical Co., 15.19 g, 0.13 mol) and 3-hydroxypyridine (19.02 g, 0.20 mol) were added to the reaction vessel, and stirred for 16 hours. Solvent was removed in vacuo. The residue was diluted with CH2Cl2 and washed with 1N NaOH. After a brine wash (2×), the organic layer was dried over MgSO4. The residue was purified by silica gel flash chromatography using a gradient from 100% CHCl3 to 10% MeOH/CHCl3 (purification system was run twice), then recrystallized with ethyl acetate to give 4.0 g (16%) of the title compound as a white powder, mp.=121-122° C. TLC Rf =0.3 1 (10%MeOH/CHCl3). MS (DCI/NH3) m/e: 193 (M+H)+ and 210 (M+NH4)+. 1H NMR (CDCl3, 300 MHz) δ: 8.32-8.30 (m, 1H), 8.27 (dd, J=4.40, 1.50 Hz, 1H), 7.25-7.16 (m, 2H), 6.17 (br s, 1H), 4.14-4.08 (m, 1H), 4.05 (dd, J=8.80, 3.70 Hz, 1H), 3.89 (dd, J=8.80, 7.70 Hz, 1H), 2.49-2.23 (m, 3H), 1.99-1.87 (m, 1H). Anal. Calc. for C10H12N2O2 : C, 62.49; H, 6.29; N, 14.57; Found C, 62.53; H, 6.25; N, 14.71.

Workup

  1. custombrought to room temperature
  2. stirringstirred for 16 hours
  3. customSolvent was removed in vacuo
  4. additionThe residue was diluted with CH2Cl2
  5. washwashed with 1N NaOH
  6. washAfter a brine wash (2×)
  7. dry with materialthe organic layer was dried over MgSO4
  8. customThe residue was purified by silica gel flash chromatography
  9. custompurification system
  10. customthen recrystallized with ethyl acetate

Sources & evidence

ORD record
ord-70a587b848254b2bb94d1bb4d54ab270
Source dataset
uspto-grants-1999_09
Patent number
US05948793

Reaction notes

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