Sodium Cyanide → (3-(4-((4-(Hydroxymethyl)-4-methylpiperidin-1-yl)methyl)-3-methylphenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

HRID 1035237Notes

Reaction equation

HRID 1035237 reaction equation
[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:21]=[CH:20][C:9]([CH2:10][N:11]3[CH2:16][CH2:15][C:14]([CH2:18][OH:19])([CH3:17])[CH2:13][CH2:12]3)=[C:8]([CH3:22])[CH:7]=2)[CH2:2]1.[C:23]1([C:29]2[O:33][C:32]([C:34](OCC)=[O:35])=[N:31][N:30]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[C-]#N.[Na+]>CO>[OH:19][CH2:18][C:14]1([CH3:17])[CH2:15][CH2:16][N:11]([CH2:10][C:9]2[CH:20]=[CH:21][C:6]([O:5][CH:3]3[CH2:4][N:1]([C:34]([C:32]4[O:33][C:29]([C:23]5[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=5)=[N:30][N:31]=4)=[O:35])[CH2:2]3)=[CH:7][C:8]=2[CH3:22])[CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 8929Sodium CyanideHCID 651752Ethyl 5-phenyl-1,3,4-oxadiazole-2-carboxylateHCID 66656363(1-(4-(Azetidin-3-yloxy)-2-methylbenzyl)-4-methylpiperidin-4-yl)methanol

Product 1

HCID 56597146(3-(4-((4-(Hydroxymethyl)-4-methylpiperidin-1-yl)methyl)-3-methylphenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanoneYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 69C (1.65 g, 5.42 mmol) in methanol (25 mL) was added commercially available ethyl 5-phenyl-1,3,4-oxadiazole-2-carboxylate (1.30 g, 5.96 mmol) followed by sodium cyanide (53 mg, 1.10 mmol). The reaction mixture was stirred at RT overnight. The solvent was removed by evaporation and the residue was dissolved in DCM. The solution was washed with NaHCO3, filtered through a phase separator and then evaporated to near dryness. Ether was added and the formed solid was filtered off and washed with ether. The product was dried in vacuo to afford 1.85 g (72%) of 69 as a crystalline solid, m. p. 167° C. 1H NMR (500 MHz, CDCl3): δ 0.96 (s, 3H), 1.31 (m, 2H), 1.52 (m, 2H) 2.28 (m, 2H), 2.34 (s, 3H), 2.51 (m, 2H), 3.38 (s, 2H), 3.40 (s, 2H), 4.31 (dd, 1H), 4.62 (dd, 1H), 4.73 (dd, 1H), 5.05 (m, 1H), 5.13 (m, 1H), 6.54 (dd, 1H), 6.60 (d, 1H), 7.18 (d, 1H), 7.53 (t, 2H), 7.59 (t, 1H), 8.17 (d, 2H), MS (APCI+) m/z 477 [M+H]+, LC purity: 99%.

Workup

  1. customThe solvent was removed by evaporation
  2. dissolutionthe residue was dissolved in DCM
  3. washThe solution was washed with NaHCO3
  4. filtrationfiltered through a phase separator
  5. customevaporated
  6. additionEther was added
  7. filtrationthe formed solid was filtered off
  8. washwashed with ether
  9. customThe product was dried in vacuo

Sources & evidence

ORD record
ord-028b85427bd149c193026308e1c5f1af
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

Loading…