Acetone → 4-(1-Hydroxy-1-methyl-ethyl)-3-methyl-benzoic acid

HRID 1405373노트

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HRID 1405373 반응식
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11].C([Li])CCC.[CH3:17][C:18]([CH3:20])=[O:19].Cl>O1CCCC1.[OH-].[Na+]>[OH:19][C:18]([C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11])([CH3:20])[CH3:17]

참가 물질

7

반응물 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 821314-Bromo-3-methylbenzoic acidHCID 178418339Butyllithium

생성물 1

HCID 681532454-(1-Hydroxy-1-methyl-ethyl)-3-methyl-benzoic acid수율 42.3%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 14798Sodium Hydroxide용매

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온도
-78 °C

실험 절차

4-Bromo-3-methyl-benzoic acid (3.96 g, 18.4 mmol) was dissolved in tetrahydrofuran (100 mL) and the solution was cooled to −78° C. n-Butyllithium in hexanes (16.2 mL of 2.5 M, 41 mmol) was added dropwise over 20 minutes. The reaction mixture was allowed to stir for 30 minutes at −78° C. and then acetone (1.35 mL, 18.4 mmol) was added in a drop-wise manner. The reaction mixture was allowed to stir for 30 minutes at −78° C., and then it was allowed to warm to room temperature. The reaction mixture was then diluted with 100 mL of 1M aqueous sodium hydroxide. The organic layer was discarded and then the aqueous layer was made acidic with 4M aqueous hydrochloric acid. The aqueous layer was then extracted 3 times with ethyl acetate. The combined extracts were dried over sodium sulfate and then evaporated to dryness. The crude material was further purified on silica gel utilizing a gradient of 0-10% methanol in dichloromethane to give 4-(1-hydroxy-1-methyl-ethyl)-3-methyl-benzoic acid (1.51 g, 42%). 1H NMR (400 MHz, DMSO) δ 12.74 (s, 1H), 7.68 (dd, J=3.9, 2.5 Hz, 2H), 7.55 (d, J=8.7 Hz, 1H), 5.06 (s, 1H), 2.56 (s, 3H), 1.51 (s, 6H).

후처리

  1. additionwas added dropwise over 20 minutes
  2. stirringto stir for 30 minutes at −78° C.
  3. temperatureto warm to room temperature
  4. extractionThe aqueous layer was then extracted 3 times with ethyl acetate
  5. dry with materialThe combined extracts were dried over sodium sulfate
  6. customevaporated to dryness
  7. customThe crude material was further purified on silica gel utilizing a gradient of 0-10% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-1321e9c13bef4f2e947e7ba23cc52e9d
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08916565B2

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