Dichloromethane → 2-(Chloromethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

HRID 588712ノート

反応式

HRID 588712 の反応式
CO[C:3]([CH:5]1[C:10](=O)[CH2:9][CH2:8][O:7][CH2:6]1)=[O:4].CCN(CC)CC.[Cl:19][CH2:20][C:21]([NH2:23])=[NH:22].C(Cl)Cl>CO>[Cl:19][CH2:20][C:21]1[NH:23][C:3](=[O:4])[C:5]2[CH2:6][O:7][CH2:8][CH2:9][C:10]=2[N:22]=1

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 356022-ChloroacetamidineHCID 14666555Methyl 4-oxooxane-3-carboxylate2 回

生成物 1

HCID 1357419472-(Chloromethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one収率 36%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒3 回

反応条件

温度
0 °C

実験手順

A mixture of crude 4-oxo-tetrahydro-pyran-3-carboxylic acid methyl ester (1780 g, 11 mol) and NEt3 (830 g, 8.2 mol) in MeOH (3560 mL) was cooled to 0° C. under N2. A solution of 2-chloro-acetamidine (567 g, 4.4 mol) in 890 mL of MeOH was added dropwise over 50 minutes. The reaction mixture was stirred at 0° C. for 30 minutes and then at about 20° C. for 16 hours. LCMS at 215 nm and TLC (DCM:MeOH=10:1) analysis showed that most of 4-oxo-tetrahydro-pyran-3-carboxylic acid methyl ester was consumed. The mixture was then filtered and concentrated to give black oil, which was subsequently purified by flash column chromatography on silica gel and eluted with DCM to give yellow solid/oil mixture, which was further triturated with MTBE (˜1200 mL) and H2O: CH3CN: EA=1:1:2 (˜600 mL) to give the title compound as a white solid (318 g). MS m/z 201.2 (M+H). CHN analysis: calculated (results). C, 47.89; (47.95), H, 4.52; (4.401), N, 13.96; (13.76).

後処理

  1. waitat about 20° C. for 16 hours
  2. customwas consumed
  3. filtrationThe mixture was then filtered
  4. concentrationconcentrated
  5. customto give black oil, which
  6. customwas subsequently purified by flash column chromatography on silica gel
  7. washeluted with DCM
  8. customto give yellow solid/oil mixture, which
  9. customwas further triturated with MTBE (˜1200 mL) and H2O

出典と根拠

ORDレコード
ord-65d4dcb4f9a74aecab55bb51d722a0f1
出典データセット
uspto-grants-2016_01
特許番号
US09227982B2

反応ノート

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