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

HRID 57420ノート

反応式

HRID 57420 の反応式
[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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 21226129Dichloromethane methanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-1b2e35acfe004190b306a9856b743c71
出典データセット
uspto-grants-2016_09
特許番号
US09434719B2

反応ノート

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