Triethylamine → (2R,3R)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acid

HRID 563344노트

반응식

HRID 563344 반응식
[Cl:1][C:2]1[C:3]([CH3:18])=[C:4]([NH:10][C@H:11]([C@@H:15]([OH:17])[CH3:16])[C:12]([OH:14])=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[N+](C1C=CC(C(NN)=O)=CC=1)([O-])=O.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C1COCC1>[Cl:1][C:2]1[C:3]([CH3:18])=[C:4]([NH:10][C@H:11]([C@H:15]([OH:17])[CH3:16])[C:12]([OH:14])=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 3693744Benzoic acid, 4-nitro-, hydrazideHCID 57908671(3-Chloro-4-cyano-2-methylphenyl)-D-threonine

생성물 1

HCID 57908625(2R,3R)-2-(3-chloro-4-cyano-2-methylphenylamino)-3-hydroxybutanoic acid수율 80%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-50 °C

실험 절차

(intermediate 1a)(8.3 g, 30.9 mmol), 4-nitrobenzohydrazide (6.16 g, 34.0 mmol) and anhydrous THF (200 mL) were placed in a 500 mL round bottomed flask and the mixture was cooled to −50° C. 1-Hydroxybenzotriazole hydrate (4.2 g, 30.9 mmol) was added to the mixture together with N-(3-Dimethylaminopropyl)-N′-ethylcarbodimide HCl (7.34 g, 38.3 mmol) at −50° C. followed by triethylamine (5.3 mL, 38.3 mmol). The reaction mixture was maintained at −15° C. and stirred for 1 h after which stirring continued overnight while the mixture slowly warmed to room temperature. After 18 h the mixture was filtered under vacuum and the residue washed with THF (50 mL). The THF solution was concentrated to ca. 20 mL, whereupon ethyl acetate (200 mL) was added followed by water (100 mL). The phases were partitioned and the organic phase washed with water (150 mL), brine (150 mL), dried (Na2SO4) and concentrated to furnish a light yellow solid as the title compound (15.9 g, 80%) that was used without further purification. 1H NMR (400 MHz, d6-acetone, δ in ppm) 9.88 (br s, 2H), 8.35 (d, J=6.7 Hz, 2H), 8.16 (d, J=6.7 Hz, 2H), 7.53 (d, J=7.5 Hz, 1H), 6.69 (d, J=7.5 Hz, 1H), 5.56 (d, J=6.6 Hz, 1H), 4.46-4.36 (m, 1H), 4.18-4.10 (m, 1H), 3.26 (s, 3H), 1.37 (d, J=7.4 Hz, 3H).

후처리

  1. temperatureThe reaction mixture was maintained at −15° C.
  2. stirringstirring
  3. waitcontinued overnight while the mixture
  4. temperatureslowly warmed to room temperature
  5. filtrationAfter 18 h the mixture was filtered under vacuum
  6. washthe residue washed with THF (50 mL)
  7. concentrationThe THF solution was concentrated to ca. 20 mL, whereupon ethyl acetate (200 mL)
  8. additionwas added
  9. customThe phases were partitioned
  10. washthe organic phase washed with water (150 mL), brine (150 mL)
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated

출처 및 근거

ORD 기록
ord-f8cc19e2b42d4132b705234e525d5fb5
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08067448B2

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