Chloroiodomethane → tert-butyl (1S)-3-chloro-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate

HRID 23222

반응식

HRID 23222 반응식
I[CH2:2][Cl:3].C[O:5][C:6](=O)[C@@H:7]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([F:16])[CH:10]=1.[Li+].CC([N-]C(C)C)C.C([Li])CCC>C1COCC1>[Cl:3][CH2:2][C:6](=[O:5])[C@@H:7]([NH:17][C:18](=[O:19])[O:20][C:21]([CH3:22])([CH3:23])[CH3:24])[CH2:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([F:16])[CH:10]=1

참가 물질

6

반응물 4

HCID 11644ChloroiodomethaneHCID 2724682Lithium diisopropylamideHCID 9836527(2S)-2-[(tert-Butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propionic acid methyl esterHCID 178418339Butyllithium

생성물 1

HCID 9923728tert-butyl (1S)-3-chloro-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

ICH2Cl (3.54 g, 1.46 mL, 19.82 mmol, 1.25 equivalent) and THF (5 mL) are added to (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,5-difluorophenyl)propanoic acid methyl ester (II, EXAMPLE 1, 5 g, 15.86 mmol, 1 equivalent). The mixture is cooled to −78° and LDA (22.3 mL, 44.60 mmol, 2.25 equivalents, 2.0M) is added dropwise maintaining an internal temperature below −60°. Once the addition is complete, the contents are stirred for 30 min at −78° at which time n-butyllithium (15.3 mL, 19.82 mmol, 1.25 equivalents; 1.3M in hexanes) is added dropwise maintaining an internal temperature below about −60°. The reaction is stirred for 30 min then quenched into 0° hydrochloric acid (IN). Ethyl acetate is added and the phases are separated and the aqueous phase is extracted with ethyl acetate. The combined organic phases are washed with saturated sodium bicarbonate, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound, NMR (DMSO-d6) δ 7.47, 7.06-7.14, 4.78, 4.49, 3.20, 2.82 and 1.40; CMR (DMSO-d6) δ 200.87, 163.74, 161.20, 142.74, 112.80, 102.13, 79.04, 58.97, 47.72, 34.95 and 28.30.

후처리

  1. temperatureThe mixture is cooled to −78°
  2. temperaturemaintaining an internal temperature below −60°
  3. additionOnce the addition
  4. additionis added dropwise
  5. temperaturemaintaining an internal temperature below about −60°
  6. customthen quenched into 0° hydrochloric acid (IN)
  7. additionEthyl acetate is added
  8. customthe phases are separated
  9. extractionthe aqueous phase is extracted with ethyl acetate
  10. washThe combined organic phases are washed with saturated sodium bicarbonate
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-f0237fc9b0f04078977d3db264c37c29
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06849750B2

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