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Citric Acid → (-)-{[(1R)-3-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}-1-methylpropyl]oxy}acetic acid tert.-butyl ester

HRID 1926933
ノート
印刷プレビュー

反応式

HRID 1926933 の反応式
C(OC(=O)COCC[C@H](O)C)(C)(C)C.[C:15]([O:19][C:20](=[O:28])[CH2:21][O:22][C@H:23]([CH3:27])[CH2:24][CH2:25][OH:26])([CH3:18])([CH3:17])[CH3:16].Cl[C:30]1[C:31]2[C:38]([C:39]3[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=3)=[C:37]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[O:36][C:32]=2[N:33]=[CH:34][N:35]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.O>[C:15]([O:19][C:20](=[O:28])[CH2:21][O:22][C@H:23]([CH3:27])[CH2:24][CH2:25][O:26][C:30]1[C:31]2[C:38]([C:39]3[CH:40]=[CH:41][C:42]([O:45][CH3:46])=[CH:43][CH:44]=3)=[C:37]([C:47]3[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=3)[O:36][C:32]=2[N:33]=[CH:34][N:35]=1)([CH3:18])([CH3:16])[CH3:17]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 311Citric AcidHCID 580168154-Chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidineHCID 58016861[(3R)-3-Hydroxybutyl]oxy-acetic acid tert.-butyl esterHCID 86637370{[(1R)-3-hydroxy-1-methylpropyl]oxy}acetic acid tert.-butyl ester

生成物 1

HCID 58016969(-)-{[(1R)-3-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}-1-methylpropyl]oxy}acetic acid tert.-butyl ester
収率 9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

Put 455 mg (2.23 mmol) {[(3R)-3-hydroxybutyl]oxy}acetic acid tert.-butyl ester (which contains up to approx. 10% {[(1R)-3-hydroxy-1-methylpropyl]oxy}acetic acid tert.-butyl ester) under argon in 5 ml THF and cool to 0° C. Add 1.15 ml (2.23 mmol) of a 2 M solution of phosphazene base P2-tert.-butyl in THF and stir for a further 10 min at RT. Then cool to 0° C. again. Add 500 mg (1.49 mmol) 4-chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine and stir overnight at RT. Then dilute with water, acidify with 10% aqueous citric acid solution and extract twice with ethyl acetate. Combine the ethyl acetate phases and wash once with satd. sodium chloride solution. Dry over magnesium sulphate and concentrate by evaporation. Purify the residue by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 9:1). 450 mg (60.1% of theor.) of the target compound is obtained. 75 mg (9.0% of theor.) of (−)-{[(1R)-3-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}-1-methylpropyl]oxy}acetic acid tert.-butyl ester is isolated as by-product (see Example 77).

後処理

  1. temperatureThen cool to 0° C. again
  2. stirringstir overnight at RT
  3. extractionextract twice with ethyl acetate
  4. washwash once with satd
  5. dry with materialDry over magnesium sulphate
  6. concentrationconcentrate by evaporation
  7. customPurify the residue by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 9:1)
  8. custom450 mg (60.1% of theor.) of the target compound is obtained

出典と根拠

ORDレコード
ord-c0b71c779bca4a71b90634025d1698ab
出典データセット
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08183246B2

反応ノート

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