Hydrochloric Acid → HCID 59403453, compound

HRID 1514192Notes

Reaction equation

HRID 1514192 reaction equation
[CH2:1]([C:5]1[C:12]([C:13]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([Cl:28])[CH:19]=3)[O:15][N:14]=2)=[CH:11][CH:10]=[CH:9][C:6]=1[C:7]#[N:8])[CH2:2][CH:3]=C.[O:29]=O.CSC.Cl>C(Cl)Cl.C1COCC1>[NH2:8][CH2:7][C:6]1[CH:9]=[CH:10][CH:11]=[C:12]([C:13]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([Cl:28])[CH:19]=3)[O:15][N:14]=2)[C:5]=1[CH2:1][CH2:2][CH2:3][OH:29]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 977OxygenHCID 1068Dimethyl SulfideHCID 59403544HCID 59403544, compound

Product 1

HCID 59403453HCID 59403453, compoundYield 18.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Through a solution of 2-(3-buten-1-yl)-3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)benzonitrile (Preparation 22) (8.26 g, 20.97 mmol) in DCM (125 ml) under Ar at −78° C. was bubbled Ar then O2 (5 min each). The ozonoliser (model 502; 75 lh−1; 0.3 A) was switched on and the orange solution ozonolised until it had turned an opaque green-grey colour (3 hrs). The ozonoliser was switched off, and O2, then Ar bubbled though the solution (10 min each). The solution was allowed to warm to RT under Ar, then concentrated in vacuo to give an opaque yellow oil. This was redissolved in dry THF (200 ml), BH3.DMS (9.96 ml, 105 mmol) added (CARE: gas evolution), and the solution stirred at RT for 18 hrs and then at 40° C. for 3 hrs. The reaction was cooled to 0° C., then 0.1M aqueous HCl (150 ml) was added cautiously (CARE: gas evolution), then allowed to stir at RT for 18 hrs. The solution was passed directly down an SCX-2 column (50 g), washing with MeOH. The product was eluted with 0.5M NH3 in MeOH; concentration in vacuo gave an orange foam 3-[2-(aminomethyl)-6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)phenyl]-1-propanol (2.73 g, 3.95 mmol, 18.9% yield). 1H NMR (400 MHz, CDCl3) δ (inter alia) 8.23 (1H, d), 8.05 (1H, dd), 7.86 (1H, d), 7.46 (1H, d), 7.34 (1H, t), 7.06 (1H, d), 4.72 (1H, sept), 4.03 (2H, s), 3.47 (2H, t), 3.27 (2H, t), 1.78 (2H, quin), 1.45 (6H, d); MS (ES) C21H2435ClN3O3 requires 401; found 402 [M+H]+.

Workup

  1. custom5 min
  2. customan opaque green-grey colour (3 hrs)
  3. customO2, then Ar bubbled though the solution (10 min each)
  4. concentrationconcentrated in vacuo
  5. customto give an opaque yellow oil
  6. waitat 40° C. for 3 hrs
  7. temperatureThe reaction was cooled to 0° C.
  8. stirringto stir at RT for 18 hrs
  9. washwashing with MeOH
  10. washThe product was eluted with 0.5M NH3 in MeOH
  11. concentrationconcentration in vacuo

Sources & evidence

ORD record
ord-57ccb234662f411782c9cbb206a770dc
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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