Cesium carbonate → (3aR,6aR)-3-(6-Chloro-2-morpholinopyrimidin-4-yl)tetrahydrofuro[3,4-d]oxazol-2(3H)-one

HRID 538924

反応式

HRID 538924 の反応式
[O:1]1[C@H:5]2[CH2:6][O:7][CH2:8][C@H:4]2[NH:3][C:2]1=[O:9].[Cl:10][C:11]1[CH:16]=[C:15](Cl)[N:14]=[C:13]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:12]=1.C([O-])([O-])=O.[Cs+].[Cs+].C([O-])(O)=O.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.[Ar]>[Cl:10][C:11]1[N:12]=[C:13]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:14]=[C:15]([N:3]2[C@@H:4]3[CH2:8][O:7][CH2:6][C@@H:5]3[O:1][C:2]2=[O:9])[CH:16]=1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27720684-(4,6-Dichloropyrimidin-2-yl)morpholineHCID 55303430(3aR,6aR)-tetrahydrofuro[3,4-d]oxazol-2(3H)-one

生成物 1

HCID 86694354(3aR,6aR)-3-(6-Chloro-2-morpholinopyrimidin-4-yl)tetrahydrofuro[3,4-d]oxazol-2(3H)-one収率 88.6%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 86694355Argon 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
85 °C

実験手順

To a solution of (3aR,6aR)-tetrahydrofuro[3,4-d]oxazol-2(3H)-one (500 mg, 3.87 mmol), 4-(4,6-dichloropyrimidin-2-yl)morpholine (1088 mg, 4.65 mmol) and Cs2CO3 (2.14 g, 6.58 mmol) in dioxane (20 mL) was added after degassing with argon 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (157 mg, 0.271 mmol) and Pd2(dba)3 (70.9 mg, 0.077 mmol) and the reaction mixture was heated for 6 h at 85° C. The reaction mixture was added to 10% aqueous NaHCO3 solution and extracted with EtOAc. Combined extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was triturated in MeOH overnight, filtered off and dried to afford the title compound as a colorless solid (1.12 g, 87%): tR=0.92 min (LC-MS 3); ESI-MS: 327, 329 [M+H]+ (LC-MS 3).

後処理

  1. extractionextracted with EtOAc
  2. washCombined extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was triturated in MeOH overnight
  7. filtrationfiltered off
  8. customdried

出典と根拠

ORDレコード
ord-bda22b43dbb34821baabd86acef054a1
出典データセット
uspto-grants-2014_10
特許番号
US08865894B2

関連ノート

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