Pentamethylbenzene → HCID 86700912, compound

HRID 1424368Notes

Reaction equation

HRID 1424368 reaction equation
C([O:8][C:9]1[C:14]2[CH:15]=[C:16]([C:18]3[N:19]=[C:20]4[N:24]([CH:25]=3)[N:23]=[C:22]([O:26][CH3:27])[S:21]4)[O:17][C:13]=2[CH:12]=[C:11]([Cl:28])[CH:10]=1)C1C=CC=CC=1.CC1C(C)=C(C)C(C)=C(C)C=1.B(Cl)(Cl)Cl.C([O-])(O)=O.[Na+]>C(Cl)Cl.CCOC(C)=O.O>[Cl:28][C:11]1[CH:12]=[C:13]2[O:17][C:16]([C:18]3[N:19]=[C:20]4[N:24]([CH:25]=3)[N:23]=[C:22]([O:26][CH3:27])[S:21]4)=[CH:15][C:14]2=[C:9]([OH:8])[CH:10]=1

Participants

8

Reactant 4

HCID 12784PentamethylbenzeneHCID 25135Boron TrichlorideHCID 516892Sodium BicarbonateHCID 86700911HCID 86700911, compound

Product 1

HCID 86700912HCID 86700912, compoundYield 66.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A stirred solution of 6-(4-(benzyloxy)-6-chlorobenzofuran-2-yl)-2-methoxyimidazo[2,1-b][1,3,4]thiadiazole (Example 37H, 0.85 g, 2.064 mmol) and pentamethylbenzene (2.142 g, 14.45 mmol) in DCM under N2 atmosphere was cooled to −78° C. after which boron trichloride (5.16 mL, 5.16 mmol) was added dropwise over ˜4 minutes. The reaction was monitored by TLC using 1:1 hexanes:EtOAc as eluent. The reaction mixture was stirred at −78° C. for 30 minutes after which a mixture of water (40 mL) and saturated NaHCO3 (5 mL) was added (at −78° C.) and the mixture was stirred until ambient temperature was obtained (removed from cooling bath). The solid precipitate was filtered off and rinsed with diethyl ether then allowed to dry overnight to give the title material (441 mgs, 1.371 mmol, 66.4% yield) as a beige solid. The filtrate was extracted with DCM. The organic phase was washed with brine, dried (MgSO4) and concentrated to dryness. The residue was purified by ISCO using DCM/EtOAc as eluent. Fractions containing the desired product were concentrated to give the title material (25 mgs, 0.078 mmol, 3.77% yield) as a beige solid. LC (Method A): 2.167 min. LCMS (APCI) calcd for C13H9ClN3O3S [M+H]+ m/z 322.00. found 322.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 10.50 (br. S, 1H), 8.45 (s, 1H), 7.17 (dd, J=0.8, 1.6 Hz, 1H), 7.09 (d, J=0.8 Hz, 1H), 6.67 (d, J=2.0 Hz, 2H), 4.21 (s, 3H).

Workup

  1. additionwas added dropwise over ˜4 minutes
  2. additionwas added (at −78° C.)
  3. stirringthe mixture was stirred until ambient temperature
  4. customwas obtained
  5. custom(removed from cooling bath)
  6. filtrationThe solid precipitate was filtered off
  7. washrinsed with diethyl ether
  8. customto dry overnight

Sources & evidence

ORD record
ord-f0dcce07380f49ea88616422a27597fe
Source dataset
uspto-grants-2015_01
Patent number
US08927688B2

Reaction notes

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