Chloroiodomethane → (R)-N-((S)-1-(4-(1-ethoxycyclopropyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

HRID 1850154노트

반응식

HRID 1850154 반응식
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([C@@H:12]([NH:14][S@@:15]([C:17]([CH3:20])([CH3:19])[CH3:18])=[O:16])[CH3:13])=[C:8]([F:21])[CH:7]=1)=[CH2:5])[CH3:2].Cl[CH2:23]I.C([Zn]CC)C.[NH4+].[Cl-]>C1(C)C=CC=CC=1.CO.C(Cl)Cl>[CH2:1]([O:3][C:4]1([C:6]2[CH:11]=[CH:10][C:9]([C@@H:12]([NH:14][S@@:15]([C:17]([CH3:19])([CH3:18])[CH3:20])=[O:16])[CH3:13])=[C:8]([F:21])[CH:7]=2)[CH2:23][CH2:5]1)[CH3:2]

참가 물질

7

반응물 4

HCID 11644ChloroiodomethaneHCID 25517Ammonium ChlorideHCID 86730184(R)-N-((S)-1-(4-(1-ethoxyvinyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamideHCID 178418750HCID 178418750, 화합물

생성물 1

HCID 86730185(R)-N-((S)-1-(4-(1-ethoxycyclopropyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide수율 28.2%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 21226129Dichloromethane methanol용매

실험 절차

To a round bottom flask containing (R)—N—((S)-1-(4-(1-ethoxyvinyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (0.49 g, 1.56 mmol) and chloroiodomethane (1.14 mL, 15.6 mmol) in toluene (15 mL) at 0° C. under argon was added diethylzinc (1.0M in hexanes) (15.6 mL, 15.6 mmol). Reaction mixture allowed to warm to room temperature and stirred for 1 hour. Reaction mixture was cooled to 0° C. in an ice bath and to the cold reaction mixture was slowly added a saturated solution of NH4Cl. The aqueous mixture was extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (MeOH/CH2Cl2 0 to 10%) provided (R)—N—((S)-1-(4-(1-ethoxycyclopropyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (145 mg, 0.44 mmol, 28% yield) as a viscous brown oil. 1H NMR (300 MHz, CDCL3) δ 0.93-0.99 (m, 2H) 1.14-1.20 (m, 3H) 1.21 (s, 9H) 1.22-1.27 (m, 2H) 1.57-1.61 (m, 4H) 3.35 (d, J=4.98 Hz, 1H) 3.45 (q, J=7.07 Hz, 2H) 4.77-4.87 (m, 1H) 6.98 (dd, J=7.58, 1.43 Hz, 3H) 7.00-7.03 (m, 4H) 7.28-7.32 (m, 1H). LCMS m/z 328.1 (M+H)+, Rt 0.95 min.

후처리

  1. customReaction mixture
  2. customReaction mixture
  3. temperaturewas cooled to 0° C. in an ice bath and to the cold reaction mixture
  4. extractionThe aqueous mixture was extracted with EtOAc
  5. washwashed with water, brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated onto silica gel

출처 및 근거

ORD 기록
ord-29a9495b58d94553b5708036a658763b
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08957068B2

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