2(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl- → Ethyl 2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)propionate

HRID 729705ノート

反応式

HRID 729705 の反応式
[Li+].CC([N-]C(C)C)C.CN1C(=O)N(C)CCC1.[CH2:18]([O:20][C:21](=[O:33])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=1)[CH3:19].I[CH2:35][CH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1>CCCCCCC.C1COCC1.C1(CC)C=CC=CC=1.C1COCC1>[CH3:32][S:29]([C:26]1[CH:27]=[CH:28][C:23]([CH:22]([CH2:35][CH:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)[C:21]([O:20][CH2:18][CH3:19])=[O:33])=[CH:24][CH:25]=1)(=[O:31])=[O:30]

参加物

7

反応物 4

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2724682Lithium diisopropylamideHCID 27955074-(Iodomethyl)oxaneHCID 12238955Ethyl 4-(methylsulfonyl)phenylacetate

生成物 1

HCID 21094178Ethyl 2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)propionate

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒3 回HCID 22742125Tetrahydrofuran heptane ethylbenzol溶媒

反応条件

温度
20 °C

実験手順

LDA (38.9 mL of a 1.8M solution in n-C7H16-THF-PhEt, 70.0 mmol) was added to a solution of DMPU (59.3 mL, 490.3 mmol) in anhydrous THF (150 mL) at −78° C. The mixture was stirred for 30 min, before being treated dropwise with a solution of ethyl(4-methanesulfonylphenyl)acetate (Preparation 15, 16.97 g, 70.0 mmol) in anhydrous THF (50 mL). Stirring was continued at −78° C. for 45 min, then a solution of 4-iodomethyltetrahydropyran (19.00 g, 84.0 mmol) in anhydrous THF (40 mL) was added. The mixture was allowed to warm to 20° C. over 16 h, before being quenched with 1M HCl (70 mL). The THF was removed under reduced pressure, then more H2O (40 mL) was added and the remainder extracted with EtOAc (2×250 mL). The EtOAc extracts were dried (MgSO4). Filtration, solvent evaporation, and flash chromatography (IH-EtOAc, 9:1 to 1:1) furnished ethyl 2-(4-methanesulfonylphenyl)-3-(tetrahydropyran-4-yl)propionate: m/z (ES+)=698.3 [2M+NH4]+. A solution of this compound (20.27 g, 59.6 mmol) in MeOH (100 mL) and 2M NaOH (62.5 mL, 125.0 mmol) was heated under reflux for 1 h. The solvents were removed under reduced pressure, then the remaining solid was triturated with Et2O (5×100 mL), before being dissolved in H2O (100 mL). The aqueous solution was washed with EtOAc (50 mL), acidified with 2M HCl to pH 1, and extracted with EtOAc (2×1 L). After drying (MgSO4), filtration and solvent evaporation gave the title compound: m/z (ES+)=642.3 [2M+NH4]+.

後処理

  1. stirringStirring
  2. waitwas continued at −78° C. for 45 min
  3. custombefore being quenched with 1M HCl (70 mL)
  4. customThe THF was removed under reduced pressure
  5. additionmore H2O (40 mL) was added
  6. extractionthe remainder extracted with EtOAc (2×250 mL)
  7. dry with materialThe EtOAc extracts were dried (MgSO4)
  8. filtrationFiltration, solvent evaporation, and flash chromatography (IH-EtOAc, 9:1 to 1:1)

出典と根拠

ORDレコード
ord-211845d307964654bc88f1a8f1aa7f5f
出典データセット
uspto-grants-2009_09
特許番号
US07582632B2

反応ノート

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