Potassium Phosphate, Tribasic → Tert-butyl 4-((2-cyanoadamantan-2-yl)methoxy)-5-cyclopropyl-2-fluorobenzoate

HRID 1849772ノート

反応式

HRID 1849772 の反応式
Cl[C:2]1[C:3]([O:16][CH2:17][C:18]2([C:28]#[N:29])[CH:25]3[CH2:26][CH:21]4[CH2:22][CH:23]([CH2:27][CH:19]2[CH2:20]4)[CH2:24]3)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH:30]1(B(O)O)[CH2:32][CH2:31]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.CC(O)=O.CC(O)=O.[Pd].O>[C:28]([C:18]1([CH2:17][O:16][C:3]2[C:2]([CH:30]3[CH2:32][CH2:31]3)=[CH:14][C:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])=[C:5]([F:15])[CH:4]=2)[CH:25]2[CH2:26][CH:21]3[CH2:22][CH:23]([CH2:27][CH:19]1[CH2:20]3)[CH2:24]2)#[N:29]

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86703653Tert-butyl 5-chloro-4-((2-cyanoadamantan-2-yl)methoxy)-2-fluorobenzoate

生成物 1

HCID 86703654Tert-butyl 4-((2-cyanoadamantan-2-yl)methoxy)-5-cyclopropyl-2-fluorobenzoate収率 89.2%

試薬・触媒・溶媒 3

HCID 4144353Palladium (II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

実験手順

To a solution of tert-butyl 5-chloro-4-((2-cyanoadamantan-2-yl)methoxy)-2-fluorobenzoate (1.12 g, 2.66 mmol) in toluene (40 mL) was added water (5 mL), cyclopropylboronic acid (1.32 g, 15.40 mmol), tribasic potassium phosphate (1.69 g, 7.94 mmol), tricyclohexylphosphine tetrafluoroborate (0.658 g, 2.13 mmol) and palladium(II) acetate trimer (0.25 g, 1.09 mmol) while degassing with argon. The reaction mixture was heated to reflux under an argon atmosphere for 16 hours, cooled to ambient temperature. The mixture was filtered through a pad of diatomaceous earth that was washed with ethyl acetate (100 mL). The filtrate was diluted with ethyl acetate (100 mL), washed with a 3:1 mixture of saturated aqueous ammonium chloride and water (150 mL), brine (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by column chromatography with a gradient of 0-10% ethyl acetate in hexanes to afford the title compound as a yellow foamy solid (1.01 g, 89%): 1H NMR (300 MHz, CDCl3) δ 7.41 (d, J=8.3 Hz, 1H), 6.51 (d, J=12.2 Hz, 1H), 4.26 (s, 2H), 2.36-2.27 (m, 4H), 2.08-2.00 (m, 2H), 1.91-1.87 (m, 5H), 1.78-1.73 (m, 4H), 1.56 (s, 9H), 0.94-0.87 (m, 2H), 0.64-0.59 (m, 2H); MS (ES−) m/z 426.1 (M+1).

後処理

  1. customwhile degassing with argon
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux under an argon atmosphere for 16 hours
  4. filtrationThe mixture was filtered through a pad of diatomaceous earth that
  5. washwas washed with ethyl acetate (100 mL)
  6. additionThe filtrate was diluted with ethyl acetate (100 mL)
  7. washwashed with a 3:1 mixture of saturated aqueous ammonium chloride and water (150 mL), brine (200 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to dryness
  11. customThe residue was purified by column chromatography with a gradient of 0-10% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-0add85cd8b46453e88aed560a2483bf3
出典データセット
uspto-grants-2015_02
特許番号
US08952169B2

反応ノート

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