Hydrochloric Acid → rac-(2'S,3'S,4'S)-6-chloro-2'-(3-chloro-2-fluoro-phenyl)-4'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-1'-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide

HRID 2065400노트

반응식

HRID 2065400 반응식
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:31])[C:10]3([CH:14]([CH2:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:13][N:12]([C:20](Cl)=[O:21])[CH:11]3[C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=3[F:30])[C:5]2=[CH:4][CH:3]=1.CC1(C)[O:37][C@@H:36]([CH2:38][CH2:39][NH2:40])[CH2:35][O:34]1.C(N(CC)CC)C.Cl>O1CCCC1>[OH:37][C@H:36]([CH2:35][OH:34])[CH2:38][CH2:39][NH:40][C:20]([N:12]1[CH2:13][CH:14]([CH2:15][C:16]([CH3:18])([CH3:17])[CH3:19])[C:10]2([C:5]3[C:6](=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[NH:8][C:9]2=[O:31])[CH:11]1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=1[F:30])=[O:21]

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 282937772-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]ethan-1-amineHCID 76776161rac-(2'S,3'S,4'S)-6-chloro-2'-(3-chloro-2-fluoro-phenyl)-4'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-1'-carbonyl chloride

생성물 1

HCID 86656667rac-(2'S,3'S,4'S)-6-chloro-2'-(3-chloro-2-fluoro-phenyl)-4'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-1'-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide수율 50%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-1′-carbonyl chloride (0.14 g, 0.28 mmol) in tetrahydrofuran (5 mL) was added 2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine prepared in Example 7 (49 mg, 0.34 mmol) and triethylamine (0.078 mL, 0.56 mmol). The reaction mixture was stirred at room temperature for 1 h. An aqueous HCl solution (1 N, 2 mL) was added. The reaction mixture was stirred at room temperature for 0.5 h. The solvents were removed and the residue was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water, brine, dried over MgSO4, and concentrated. The residue was triturated with dichlormethane and hexanes to give rac-(2′S,3′S,4′S)-6-chloro-2′-(3-chloro-2-fluoro-phenyl)-4′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-1′-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide as a white solid (Yield 75 mg, 50%).

후처리

  1. stirringThe reaction mixture was stirred at room temperature for 0.5 h
  2. customThe solvents were removed
  3. customthe residue was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washwashed with water, brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was triturated with dichlormethane and hexanes

출처 및 근거

ORD 기록
ord-4e7e24b338944399b6a125b7d8f521ef
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288431B2

반응 노트

불러오는 중…