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

HRID 713009

반응식

HRID 713009 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

반응 조건

온도
-78 °C

실험 절차

4-Bromo-3-methylbenzoic 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 dropwise manner. The reaction mixture was allowed to stir for 30 minutes at −78° C., and then allowed to warm to room temperature. The reaction mixture was then diluted with 1M aqueous sodium hydroxide (100 mL). The organic layer was discarded and then the aqueous layer was acidified 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 concentrated in vacuo. The crude material was purified by silica gel column chromatography using 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. concentrationconcentrated in vacuo
  7. customThe crude material was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-4ea9f53c876f4bdbbbdd547a63f80165
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181273B2

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