Tetrahydrofuran → tert-butyl 5-chloro-1-((5R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylate

HRID 529065노트

반응식

HRID 529065 반응식
C([O:4][CH:5]1[C:9]2[N:10]=[CH:11][N:12]=[C:13]([N:14]3[C:34]4[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=4)[C:16]4([CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]4)[CH2:15]3)[C:8]=2[C@H:7]([CH3:36])[CH2:6]1)(=O)C.C1COCC1.O[Li].O>O>[Cl:35][C:31]1[CH:30]=[C:29]2[C:16]3([CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21]3)[CH2:15][N:14]([C:13]3[C:8]4[C@H:7]([CH3:36])[CH2:6][CH:5]([OH:4])[C:9]=4[N:10]=[CH:11][N:12]=3)[C:34]2=[CH:33][CH:32]=1

참가 물질

5

반응물 3

HCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 69810145HCID 69810145, 화합물

생성물 1

HCID 69809362tert-butyl 5-chloro-1-((5R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylate수율 42%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

A solution of tert-butyl 1-((5R)-7-acetoxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-5-chlorospiro[indoline-3,4′-piperidine]-1′-carboxylate (0.170 g, 0.331 mmol) in 2:1 THF:H2O (1.8 mL) was cooled to about 0° C. LiOH—H2O (0.034 g, 0.83 mmol) was added and the reaction was stirred at about room temperature for 4 hours. The reaction was quenched by the addition of 1N HCl to pH 6. The aqueous phase was extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The crude residue was purified by column chromatography (30-70% EtOAc/Hexane) to yield tert-butyl 5-chloro-1-((5R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.065 g, 42%). LCMS (APCI+) m/z 471, 473 [M+H]+; Rt=3.82 min.

후처리

  1. customThe reaction was quenched by the addition of 1N HCl to pH 6
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washThe combined organics were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by column chromatography (30-70% EtOAc/Hexane)

출처 및 근거

ORD 기록
ord-e51f08ec6ae44c09a9cb5bd74b677d1b
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346805B2

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