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 529065Notes

Reaction equation

HRID 529065 reaction equation
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

Participants

5

Reactant 3

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

Product 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'-carboxylateYield 42%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-e51f08ec6ae44c09a9cb5bd74b677d1b
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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