2-Chlorotoluene → [4-(1,3,4-oxadiazol-2-yl)phenyl]boronic Acid

HRID 1865165

반응식

HRID 1865165 반응식
[Li].ClC1C=CC=CC=1C.Br[C:11]1[CH:16]=[CH:15][C:14]([C:17]2[O:18][CH:19]=[N:20][N:21]=2)=[CH:13][CH:12]=1.C([Li])CCCCC.C[O:30][B:31](OC)[O:32]C>C1COCC1.C1(C2C=CC=CC=2)C=CC=CC=1.CC(C)CC(=O)C.CO>[O:18]1[CH:19]=[N:20][N:21]=[C:17]1[C:14]1[CH:15]=[CH:16][C:11]([B:31]([OH:32])[OH:30])=[CH:12][CH:13]=1

참가 물질

10

반응물 5

HCID 72382-ChlorotolueneHCID 8470Trimethyl borateHCID 7151202-(4-Bromophenyl)-1,3,4-oxadiazoleHCID 3028194LithiumHCID 178506865HCID 178506865, 화합물

생성물 1

HCID 10219751[4-(1,3,4-oxadiazol-2-yl)phenyl]boronic Acid수율 60%

시약·촉매·용매 4

HCID 7095Biphenyl촉매HCID 887Methanol용매HCID 7909Methyl Isobutyl Ketone용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-30 °C

실험 절차

Tetrahydrofuran (250 g) was charged to a mixture of lithium granules (3.02 g) and biphenyl (0.01 g) under an argon atmosphere and the mixture cooled to −30° C. 2-Chlorotoluene (27.55 g) was slowly added at −30° C. The reaction was held at −30° C. for 6 hours and then cooled to −65° C. A mixture of 2-(4-bromophenyl)-1,3,4-oxadiazole (50.0 g) in THF (300 g) was slowly added at −65° C. The reaction was held at −65° C. for 30 minutes then a solution of n-hexyllithium (33% w/w in hexanes, 86 ml) was added at −65° C. The reaction was held at −65° C. for 30 minutes and then trimethylborate (48.7 g) was added at −65° C. The reaction was held at −65° C. for 10 minutes then methanol (55.3 g) was added followed by 4-methyl-2-pentanone (240 g). The reaction mixture was warmed and the low boiling solvents distilled off under vacuum to a maximum temperature of 55° C. The residual mixture was cooled to 0° C. and 10% w/w sulphuric acid (92 g) was added followed by water (92 g) whilst maintaining the temperature below 7° C. Product precipitated. The pH was adjusted to 6.5 by the addition of more 10% w/w sulphuric acid (85.3 g). The mixture was heated to 40° C. then cooled back to 5-10° C. Product was isolated and washed with THF (56 g) and water (60 g), yielding wet title compound (25.2 g, 60%).

후처리

  1. temperaturecooled to −65° C
  2. additionwas slowly added at −65° C
  3. waitThe reaction was held at −65° C. for 30 minutes
  4. waitThe reaction was held at −65° C. for 30 minutes
  5. waitThe reaction was held at −65° C. for 10 minutes
  6. temperatureThe reaction mixture was warmed
  7. distillationthe low boiling solvents distilled off under vacuum to a maximum temperature of 55° C
  8. temperatureThe residual mixture was cooled to 0° C.
  9. addition10% w/w sulphuric acid (92 g) was added
  10. temperaturewhilst maintaining the temperature below 7° C
  11. customProduct precipitated
  12. additionThe pH was adjusted to 6.5 by the addition of more 10% w/w sulphuric acid (85.3 g)
  13. temperatureThe mixture was heated to 40° C.
  14. temperaturethen cooled back to 5-10° C
  15. customProduct was isolated
  16. washwashed with THF (56 g) and water (60 g)

출처 및 근거

ORD 기록
ord-72daac1cb498489f821f0afb99bf6bee
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07626020B2

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