4'-Fluoroacetophenone → 3-(4-Acetylphenoxy)-5-[(1S)-2-methoxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 20596

反応式

HRID 20596 の反応式
[OH:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@@H:18]([CH3:22])[CH2:19][O:20][CH3:21])[CH:16]=1)[C:5]([NH:7][C:8]1[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=1)=[O:6].CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.C([O-])(=O)C1C=CC=CC=1.[K+].[CH3:51][C:52]([C:54]1[CH:59]=[CH:58][C:57](F)=[CH:56][CH:55]=1)=[O:53]>CN1C(=O)CCC1>[C:52]([C:54]1[CH:59]=[CH:58][C:57]([O:1][C:2]2[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@@H:18]([CH3:22])[CH2:19][O:20][CH3:21])[CH:16]=2)[C:5]([NH:7][C:8]2[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=2)=[O:6])=[CH:56][CH:55]=1)(=[O:53])[CH3:51]

参加物

6

反応物 4

HCID 98284'-FluoroacetophenoneHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 23661960Potassium BenzoateHCID 591271783-hydroxy-5-{[(2S)-1-methoxypropan-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

生成物 1

HCID 593469153-(4-Acetylphenoxy)-5-[(1S)-2-methoxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide収率 49.8%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
200 °C

実験手順

A mixture of 3-hydroxy-5-[(1S)-2-methoxy-(1-methylethyl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (400 mg, 1.31 mmol), PS-BEMP (2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diaza-phosphorine, polymer-bound, loading 2.2 mmol/g) (894 mg, 1.97 mmol), potassium benzoate (210 mg, 1.31 mmol) and 4-fluoroacetophenone (0.160 mL, 1.31 mmol) in NMP (10 mL) was heated to 200° C. in a ‘Smith Creator’ microwave for 1 hour. The polymer supported base was filtered off and the resin washed with ethyl acetate (100 mL). The organic phase was partioned with water (100 mL) at which point brine had to be added to resolve the layers. The aqueous phase was washed twice with ethyl acetate (50 mL) and then discarded. The combined organic extracts were Washed with saturated aqueous lithium chloride solution (2×100 mL), 2M sodium hydroxide solution (2×100 mL), water (2×100 mL), brine (100 mL) and dried (MgSO4). The volatiles were removed and the resulting oil purified by on silica, eluting with 0-100% ethyl acetate in iso-hexane, to give the desired product as a colourless foam (276 mg).

後処理

  1. filtrationwas filtered off
  2. washthe resin washed with ethyl acetate (100 mL)
  3. additionto be added
  4. washThe aqueous phase was washed twice with ethyl acetate (50 mL)
  5. washThe combined organic extracts were Washed with saturated aqueous lithium chloride solution (2×100 mL), 2M sodium hydroxide solution (2×100 mL), water (2×100 mL), brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. customThe volatiles were removed
  8. customthe resulting oil purified by on silica
  9. washeluting with 0-100% ethyl acetate in iso-hexane

出典と根拠

ORDレコード
ord-4ea3f68f179a453cb72b5e8359f2e37d
出典データセット
uspto-grants-2010_06
特許番号
US07745475B2

関連ノート

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