Potassium Carbonate → (R)-2-[4-(4-Thiophen-3-yl-benzoyl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 750066ノート

反応式

HRID 750066 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21](=[O:29])[C:22]2[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[S:30]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21](=[O:29])[C:22]2[CH:27]=[CH:26][C:25]([C:32]3[CH:33]=[CH:34][S:30][CH:31]=3)=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

9

反応物 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 581760Thiophene-3-boronic acidHCID 44221510(R)-2-[4-(4-Iodo-benzoyl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 68999764(R)-2-[4-(4-Thiophen-3-yl-benzoyl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester収率 60%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 702Ethanol溶媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

To a 25 mL press resistant vial which contained a suspension of (R)-2-[4-(4-Iodo-benzoyl)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (250 mg, 0.5 mmol), thiophene-3-boronic acid (130 mg, 1 mmol), palladium(II) acetate (20 mg, 0.1 mmol) and triphenyl phosphine (60 mg, 0.25 mmol) in DME (10 mL) was added potassium carbonate (500 mg, 3 mmol), ethanol (1 mL) and water (1 mL) at rt. The tube was sealed and the mixture was allowed to stir at rt for 30 min and then was heated to 98° C. and stirred at 98° C. for 16 h. After cooling to rt, the mixture was poured onto 200 mL ice-water solution and then extracted with EtOAc (3×30 mL). The combined organic layers were washed with water (2×30 mL) and brine (20 mL). and dried over anhy. Na2SO4. The solvent was removed in vacuo to obtain the crude product which was purified by silica gel flash chromatography to afford title product, (130 mg, 60%); 1H NMR (400 MHz, CDCl3); δ 1.48 (s, 9H), 1.81-2.10 (m, 4H), 3.30-3.48 (m, 2H), 3.87-4.10 (m, 1H), 4.10-4.30 (m, 2H), 6.98-7. (m, 2H), 7.42-7.48 (m, 2H), 7.58-7.60 (m, 1H), 7.70 (d, J=8.4 Hz, 2H), 7.80-7.84 (m, 4H):

後処理

  1. customThe tube was sealed
  2. temperaturewas heated to 98° C.
  3. stirringstirred at 98° C. for 16 h
  4. temperatureAfter cooling to rt
  5. extractionextracted with EtOAc (3×30 mL)
  6. washThe combined organic layers were washed with water (2×30 mL) and brine (20 mL)
  7. customand dried over anhy
  8. customThe solvent was removed in vacuo
  9. customto obtain the crude product which
  10. customwas purified by silica gel flash chromatography

出典と根拠

ORDレコード
ord-bc8e7491f38b4146996ca8c4b5e9b3de
出典データセット
uspto-grants-2008_07
特許番号
US07402684B2

反応ノート

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