Potassium Phosphate, Tribasic → Tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-ylmethoxy)-5-cyclopropyl-2-fluorobenzoate

HRID 1849739ノート

反応式

HRID 1849739 の反応式
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([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)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[CH:28]1(B(O)O)[CH2:30][CH2:29]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([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)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1

参加物

9

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86703617Tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-ylmethoxy)-5-chloro-2-fluorobenzoate

生成物 1

HCID 86703618Tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-ylmethoxy)-5-cyclopropyl-2-fluorobenzoate収率 259.1%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
150 °C

実験手順

To a mixture of tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-ylmethoxy)-5-chloro-2-fluorobenzoate (1.20 g, 3.00 mmol) in toluene (18 mL) was added cyclopropylboronic acid (1.55 g, 18.00 mmol), potassium phosphate tribasic (1.91 g, 9.00 mmol), tricyclohexyl- phosphine tetrafluoroborate (0.884 g, 2.40 mmol), palladium acetate (0.269 g, 1.20 mmol) and water (2 mL). The reaction mixture was thoroughly degassed by passing argon through it and then heated in a microwave at 150° C. for 30 minutes. The reaction was performed 4 times as described. After cooling to ambient temperature, the reaction mixtures were combined, diluted with ethyl acetate (200 mL) and filtered over anhydrous sodium sulfate. After removing all volatiles under reduced pressure, the residue was purified by silica gel column chromatography using 0-30% ethyl acetate in hexanes as eluent to afford the title compound as a yellowish oil (3.16 g, 16%): 1H NMR (300 MHz, CDCl3) δ 7.35 (d, J=8.4 Hz, 1H), 6.48 (d, J=12.7 Hz, 1H), 3.95-3.92 (m, 4H), 3.80 (d, J=6.1 Hz, 2H), 2.04-1.70 (m, 10H), 1.54 (s, 9H), 0.91-0.82 (m, 2H), 0.64-0.57 (m, 2H).

後処理

  1. customThe reaction mixture was thoroughly degassed
  2. temperatureAfter cooling to ambient temperature
  3. customthe reaction mixtures
  4. filtrationfiltered over anhydrous sodium sulfate
  5. customAfter removing all volatiles under reduced pressure
  6. customthe residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-6e4a47ef2b014429a016647758e186b3
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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