Ethyl Acetate → (2S,3S)-2-(4-Chlorophenyl)-3,5,5-trimethylmorpholin-2-ol

HRID 1399531노트

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HRID 1399531 반응식
[CH3:1][C@H:2]1[C:7](=[O:8])[O:6][CH2:5][C:4]([CH3:10])([CH3:9])[NH:3]1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([Mg]Br)=[CH:14][CH:13]=1.[NH4+].[Cl-].CCOC(C)=O>C1COCC1>[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([C@:7]2([OH:8])[O:6][CH2:5][C:4]([CH3:10])([CH3:9])[NH:3][C@H:2]2[CH3:1])=[CH:14][CH:13]=1

참가 물질

6

반응물 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 46837646HCID 46837646, 화합물HCID 178478191HCID 178478191, 화합물

생성물 1

HCID 46837780(2S,3S)-2-(4-Chlorophenyl)-3,5,5-trimethylmorpholin-2-ol수율 29%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-78 °C

실험 절차

A solution of 15 (357 mg, 2.50 mmol) in dry THF (2.5 mL, 1M) under an N2 atmosphere was cooled to −78° C. and treated with 4-chlorophenylmagnesium bromide (2 equiv., 5.00 mmol, 5.00 mL, 1M solution in ether). The reaction mixture was stirred at −78° C. for 2 h. A saturated aqueous solution of NH4Cl was added to the reaction vessel, and the mixture was allowed to warm to room temperature. EtOAc was added and the organic layer was separated and the aqueous phase was extracted with EtOAc (trice). The combined organic extracts were washed (water, brine), dried (Na2SO4) and concentrated. The residue was purified by column chromatography on silica gel using CH2Cl2 to CH2Cl2-MeOH (90:10) as the eluent to afford 180 mg (29%) of 4i as a white solid: [α]23D +33° (c 0.4, CHCl3): 1H NMR (CDCl3) δ 7.54 (d, 2H, J=8.5 Hz), 7.32 (d, 2H, J=8.5 Hz), 3.83 (d, 1H, J=11.3 Hz), 3.40 (d, 1H, J=11.3 Hz), 3.18 (q, 1H, J=6.5 Hz), 1.38 (s, 3H), 1.08 (s, 3H), 0.78 (d, 3H, J=6.5 Hz); 13C NMR (CDCl3) δ 128.5, 128.1, 127.6, 127.2, 101.6, 95.9, 69.5, 53.4, 49.7, 27.3, 22.8, 16.4; LCMS (ESI) m/z 256.3 [(M+H)+, M=C13H18ClNO2].

후처리

  1. temperatureto warm to room temperature
  2. customthe organic layer was separated
  3. extractionthe aqueous phase was extracted with EtOAc (trice)
  4. washThe combined organic extracts were washed (water, brine)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel

출처 및 근거

ORD 기록
ord-320f760ddc494641a774dd44b931b548
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906908B2

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