Hydrochloric Acid → HCID 59403544, compound

HRID 1514191Notes

Reaction equation

HRID 1514191 reaction equation
C(NC(C)C)(C)C.[Li][CH2:9][CH2:10][CH2:11][CH3:12].[Cl:13][C:14]1[CH:15]=[C:16]([C:24]2[O:28][N:27]=[C:26]([C:29]3[C:30](C)=[C:31]([CH:34]=[CH:35][CH:36]=3)[C:32]#[N:33])[N:25]=2)[CH:17]=[CH:18][C:19]=1[O:20][CH:21]([CH3:23])[CH3:22].C(Br)C=C.Cl.CCCC(C)C>C1COCC1.C(Cl)Cl>[CH2:9]([C:30]1[C:29]([C:26]2[N:25]=[C:24]([C:16]3[CH:17]=[CH:18][C:19]([O:20][CH:21]([CH3:22])[CH3:23])=[C:14]([Cl:13])[CH:15]=3)[O:28][N:27]=2)=[CH:36][CH:35]=[CH:34][C:31]=1[C:32]#[N:33])[CH2:10][CH:11]=[CH2:12]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 7841Allyl bromideHCID 78922-MethylpentaneHCID 7912DiisopropylamineHCID 59403465HCID 59403465, compoundHCID 178418339Butyllithium

Product 1

HCID 59403544HCID 59403544, compoundYield 59.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of diisopropylamine (15.15 ml, 106 mmol) in dry THF (650 m) at −78° C. under Ar was added nBuLi (44.3 ml, 70.9 mmol) down the side of the flask and the resulting solution stirred for 1 h. A solution of 3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2-methylbenzonitrile Preparation 21) (12.54 g, 35.4 mmol) in dry THF (100 ml) under Ar was added dropwise at ˜10 mlmin−1, and the resulting dark blue solution stirred at −78° C. for 45 min. Allyl bromide (6.13 ml, 70.9 mmol) was added dropwise at ˜3 mlmin−1, and the resulting dark red solution stirred for 30 min at −78° C. 1 M HCl (aq) (375 ml) was added, the mixture allowed to warm to RT then the layers separated. The aqueous was extracted with EtOAc (2×125 ml), then the combined organics washed with brine (250 ml), dried (MgSO4), filtered and concentrated in vacuo to give a crude red oil (12.8 g). This was redissolved in DCM (20 ml) and added to a pre-wet (isohexane) column of silica (5 cm×5 cm). Elution with EtOAc-isohexane (1:3) and concentration of the desired fractions gave a pale orange solid 2-(3-buten-1-yl)-3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)benzonitrile (9.50 g, 20.98 mmol, 59.2% yield). 1H NMR (400 MHz, CDCl3) δ 8.26 (1H, d), 8.24 (1H, d), 8.05 (1H, dd), 7.79 (1H, d), 7.46 (1H, t), 7.07 (1H, d), 5.94 (1H, ddt), 5.07 (1H, dq), 5.01 (1H, dd), 4.73 (1H, sept), 3.40 (2H, t), 2.47 (2H, qd), 1.45 (6H, d); MS (ES) C22H2035ClN3O2 requires 393; found 394 [M+H]+.

Workup

  1. additionwas added dropwise at ˜10 mlmin−1
  2. stirringthe resulting dark blue solution stirred at −78° C. for 45 min
  3. stirringthe resulting dark red solution stirred for 30 min at −78° C
  4. customthe layers separated
  5. extractionThe aqueous was extracted with EtOAc (2×125 ml)
  6. washthe combined organics washed with brine (250 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a crude red oil (12.8 g)
  11. washElution with EtOAc-isohexane (1:3) and concentration of the desired fractions

Sources & evidence

ORD record
ord-5b872406a58a4882a43bcb8b486df95b
Source dataset
uspto-grants-2012_07
Patent number
US08222245B2

Reaction notes

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