(-)-Epichlorohydrin → HCID 86650521, compound

HRID 1958831Notes

Reaction equation

HRID 1958831 reaction equation
[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH2:21][N:22]([CH2:24][CH3:25])[CH3:23])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:26])[C:4]=1[OH:27])[CH3:2].[CH2:28]([C@@H:30]1[O:32][CH2:31]1)Cl>C(O)(C)C.[OH-].[Na+]>[CH2:24]([N:22]([CH2:21][C:16]1[CH:17]=[C:18]([CH3:20])[CH:19]=[C:14]([C:12]2[O:11][N:10]=[C:9]([C:7]3[CH:6]=[C:5]([CH3:26])[C:4]([O:27][CH2:28][C@@H:30]4[CH2:31][O:32]4)=[C:3]([CH2:1][CH3:2])[CH:8]=3)[N:13]=2)[CH:15]=1)[CH3:23])[CH3:25]

Participants

5

Reactant 2

HCID 2734062(-)-EpichlorohydrinHCID 136331245HCID 136331245, compound

Product 1

HCID 86650521HCID 86650521, compound

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a bi-phasic mixture of 2-ethyl-4-(5-{3-[(ethyl-methyl-amino)-methyl]-5-methyl-phenyl}-[1,2,4]oxadiazol-3-yl)-6-methyl-phenol (1.74 g, 4.76 mmol) in isopropanol (100 mL) and 3M aq. NaOH (23 mL), (R)-epichlorohydrin (4.40 g, 47.6 mmol) is added. The mixture is stirred at rt for 16 h before it is concentrated to about half its volume. The remaining solution is extracted with EA, the org. extract is washed with 1M aq. NaOH followed by water. The washings are extracted back with EA. The combined org. extracts are dried over Na2SO4, filtered and concentrated. The crude product is purified by prep. HPLC (Waters XBridge Prep C18, 50×150 mm ID, 10 μm, eluting with a gradient of MeCN in water containing 0.5% of sat. aq. ammonia) to give ethyl-{3-[3-((S)-3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-5-methyl-benzyl}-methyl-amine as a colourless resin (950 mg). LC-MS*: tR=1.26 min; [M+1]+=422.23; 1H NMR (D6-DMSO): δ 1.06 (t, J=7.0 Hz, 3H), 1.24 (t, J=7.5 Hz, 3H), 2.14 (s, 3H), 2.36 (s, 3H), 2.41-2.48 (m, 5H), 2.69-2.78 (m, 3H), 2.86 (t, J=5.0 Hz, 1H), 3.37-3.42 (m, 1H), 3.54 (s, 2H), 3.69 (dd, J=11.0, 6.8 Hz, 1H), 4.21 (dd, J=11.3, 2.5 Hz, 1H), 7.47 (s, 1H), 7.80 (s, 2H), 7.90 (s, 1H), 7.92 (s, 1H).

Workup

  1. additionis added
  2. concentrationis concentrated to about half its volume
  3. extractionThe remaining solution is extracted with EA
  4. extractionextract
  5. washis washed with 1M aq. NaOH
  6. extractionThe washings are extracted back with EA
  7. dry with materialextracts are dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product is purified by prep
  11. washHPLC (Waters XBridge Prep C18, 50×150 mm ID, 10 μm, eluting with a gradient of MeCN in water containing 0.5% of sat. aq. ammonia)

Sources & evidence

ORD record
ord-a120cf580890460c8ecdb02c9e52b875
Source dataset
uspto-grants-2013_04
Patent number
US08410151B2

Reaction notes

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