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 2065400ノート

反応式

HRID 2065400 の反応式
[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]

参加物

6

反応物 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

生成物 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)-amide収率 50%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-4e7e24b338944399b6a125b7d8f521ef
出典データセット
uspto-grants-2012_10
特許番号
US08288431B2

反応ノート

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