Methanol → 4-[4-(4-Chlorophenoxy)phenylthiomethyl]-tetrahydropyran-4-carboxylic acid methyl ester

HRID 1584393노트

반응식

HRID 1584393 반응식
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([S:13][CH2:14][C:15]3([C:21]([OH:23])=[O:22])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[C:26](Cl)(=O)C(Cl)=O.CO.C(N(CC)CC)C>CN(C)C=O.C(Cl)Cl>[CH3:26][O:22][C:21]([C:15]1([CH2:14][S:13][C:10]2[CH:9]=[CH:8][C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:25][CH:24]=3)=[CH:12][CH:11]=2)[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:23]

참가 물질

7

반응물 4

HCID 887MethanolHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 109488734-((4-(4-chlorophenoxy)phenylthio)methyl)tetrahydro-2H-pyran-4-carboxylic acid

생성물 1

HCID 700515204-[4-(4-Chlorophenoxy)phenylthiomethyl]-tetrahydropyran-4-carboxylic acid methyl ester

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매

실험 절차

To a solution of 4-[4-(4-chlorophenoxy)phenylthiomethyl]tetrahydropyran-4-carboxylic acid (580 mg, 1.53 mmol) and N,N-dimethylformamide catalyst (22 μL) in methylene chloride (15 mL) at 0° C. was added oxalyl chloride (0.33 mL, 3.83 mmol) dropwise over 10 minutes. The mixture was warmed to room temperature over 1 hour, the partial slurry stirred an additional 12 hours, and concentrated in vacuo until the theoretical mass of the acid chloride was obtained. The residue was suspended intetrahydrofuran (7.5 mL), and methanol (0.19 mL, 4.59 mmol), followed by triethylamine (0.64 mL, 4.59 mmol) was added. The mixture was heated to reflux for 14 hours, concentrated, and the resulting residue partitioned between methylene chloride (150 mL) and 1M aqueous hydrochloric acid (50 mL). The aqueous layer was back extracted with additional portions of methylene chloride (2×30 mL), the combined extracts dried over magnesium sulfate, and concentrated to afford crude 4-[4-(4-chlorophenoxy)phenylthiomethyl]-tetrahydropyran-4-carboxylic acid methyl ester, which was taken directly into the next reaction without further purification. 1HNMR (CDCl3) δ 1.62. (m, 2H), 2.15 (dm, J=13.6 Hz, 2H), 3.13 (s, 2H), 3.47 (td, J=11.9, 2.4 Hz, 2H), 3.59 (s, 3H), 3.81 (dt, J=12.0, 4.1 Hz, 2H), 6.92 (d, J=8.9 Hz, 2H), 7.29 (d, J=8.8 Hz, 2H), 7.36 (d, J=8.8 Hz, 2H).

후처리

  1. concentrationconcentrated in vacuo until the theoretical mass of the acid chloride
  2. customwas obtained
  3. additionwas added
  4. temperatureThe mixture was heated
  5. temperatureto reflux for 14 hours
  6. concentrationconcentrated
  7. customthe resulting residue partitioned between methylene chloride (150 mL) and 1M aqueous hydrochloric acid (50 mL)
  8. extractionThe aqueous layer was back extracted with additional portions of methylene chloride (2×30 mL)
  9. dry with materialthe combined extracts dried over magnesium sulfate
  10. concentrationconcentrated

출처 및 근거

ORD 기록
ord-a97966b93a3e4a3fb3134f98aab24c15
출처 데이터셋
uspto-grants-1999_08
특허 번호
US05932595

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