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

HRID 729705

반응식

HRID 729705 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매3회HCID 22742125Tetrahydrofuran heptane ethylbenzol용매

반응 조건

온도
20 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-211845d307964654bc88f1a8f1aa7f5f
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07582632B2

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