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

HRID 1869721

反応式

HRID 1869721 の反応式
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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

ICH2Cl (3.54 g, 1.46 mL, 19, 0.82 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, 2.0 M) 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 (1N). 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.

後処理

  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 (1N)
  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

出典と根拠

ORDレコード
ord-b40be63e10f241fd95e0e0c78d063252
出典データセット
uspto-grants-2009_12
特許番号
US07638646B2

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