Potassium Phosphate, Tribasic → Tert-butyl 4-(adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoate

HRID 1427833노트

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HRID 1427833 반응식
[C:1]12([CH2:11][O:12][C:13]3[C:25](Cl)=[CH:24][C:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[C:15]([F:27])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH:28]1(B(O)O)[CH2:30][CH2:29]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]12([CH2:11][O:12][C:13]3[C:25]([CH:28]4[CH2:30][CH2:29]4)=[CH:24][C:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[C:15]([F:27])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86702858Tert-butyl 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluorobenzoate

생성물 1

HCID 86702860Tert-butyl 4-(adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluorobenzoate수율 86.1%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매2회HCID 1140Toluene용매

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온도
100 °C

실험 절차

To a solution of tert-butyl 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluorobenzoate (15.80 g, 40.00 mmol), cyclopropylboronic acid (5.16 g, 60.00 mmol) and potassium phosphate (38.20 g, 180.00 mmol) in toluene (160 mL) and water (8 mL) was bubbled with a nitrogen atmosphere for 10 min, tricyclohexylphosphine tetrafluoroborate (1.47 g, 3.99 mmol) and palladium acetate (0.45 g, 2.00 mmol) was added to this reaction mixture. The reaction mixture was heated to 100° C. for 18 h and then cooled to ambient temperature. Water (100 mL) was added and the mixture was extracted with ethyl acetate (100 mL×3), the combined organics were washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (5% ethyl acetate in hexanes) afforded the title compound as a colorless solid (13.8 g, 86%): 1H NMR (300 MHz, CDCl3) δ 7.37 (d, J=8.4 Hz, 1H), 6.47 (d, J=12.9 Hz, 1H), 3.49 (s, 2H), 2.05-1.95 (m, 4H), 1.78-1.61 (m, 12H), 1.55 (s, 9H), 0.91-0.84 (m, 2H), 0.64-0.58 (m, 2H).

후처리

  1. temperaturecooled to ambient temperature
  2. extractionthe mixture was extracted with ethyl acetate (100 mL×3)
  3. washthe combined organics were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by column chromatography (5% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-21b8a2dd0eb242c6a05e297db28f4b91
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08933236B2

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