Dichloromethane → (R)-N-((S)-1-(4-(1-ethoxyvinyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

HRID 57437

反応式

HRID 57437 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][S@@:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])[CH3:9])=[C:4]([F:17])[CH:3]=1.C([Sn](CCCC)(CCCC)[C:23]([O:25][CH2:26][CH3:27])=[CH2:24])CCC.C(Cl)Cl.C(O)(C(F)(F)F)=O.C(OC=C)=C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCOC(C)=O.CCCCCCC.C1(C)C=CC=CC=1>[CH2:26]([O:25][C:23]([C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][S@@:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])[CH3:9])=[C:4]([F:17])[CH:3]=1)=[CH2:24])[CH3:27]

参加物

9

反応物 5

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 8024Vinyl etherHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 86730183(R)-N-((S)-1-(4-bromo-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

生成物 1

HCID 86730184(R)-N-((S)-1-(4-(1-ethoxyvinyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide収率 62%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 1140Toluene溶媒HCID 21899848Ethylacetate heptane溶媒

反応条件

温度
100 °C

実験手順

To a microwave vial with stir bar was added (R)—N—((S)-1-(4-bromo-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (1 g, 3.10 mmol) followed by the addition of tributyl(1-ethoxyvinyl)stannane (2.24 g, 6.21 mmol), TEA (1.3 mL, 9.31 mmol) and PdCl2(dppf).CH2Cl2 adduct (0.127 g, 0.155 mmol). To the solids was then added toluene (10 mL). Vial capped and heated by microwave irradiation at 100° C. for 30 min. To this reaction mixture was added 1 ml of TFA to try to convert vinyl ether to the ketone which was unsuccessful. Resulting reaction mixture allowed to stir 5 min at room temperature. Reaction mixture was then quenched with a saturated solution of NaHCO3 to pH 8. Aqueous mixture extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 40 to 100%) provided (R)—N—((S)-1-(4-(1-ethoxyvinyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (0.60 g, 1.91 mmol, 62% yield) as a yellow viscous residue. 1H NMR (400 MHz, CDCl3) δ 1.20 (s, 9H) 1.43 (t, J=6.94 Hz, 3H) 1.56-1.63 (m, 5H) 3.36 (d, J=3.13 Hz, 1H) 3.92 (q, J=6.96 Hz, 2H) 4.23 (br. s., 1H) 4.65 (s, 1H) 4.79-4.91 (m, 1H) 7.30 (s, 2H) 7.40 (d, J=8.02 Hz, 1H).

後処理

  1. customVial capped
  2. customResulting
  3. customreaction mixture
  4. stirringto stir 5 min at room temperature
  5. customReaction mixture
  6. customwas then quenched with a saturated solution of NaHCO3 to pH 8
  7. extractionAqueous mixture extracted with EtOAc
  8. washwashed with water, brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated onto silica gel

出典と根拠

ORDレコード
ord-89bc929a44bd494b8f03f66daff8e049
出典データセット
uspto-grants-2016_09
特許番号
US09434719B2

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