Isopropanol → HCID 68762560, compound

HRID 529077Notes

Reaction equation

HRID 529077 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[CH:3]=1.[Li]CCCC.CCCCCC.CON(C)[C:23]([C:25]1[CH:26]=[C:27]2[C:33]3([CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)[CH2:32][N:31]([C:46]3[C:47]4[C@H:54]([CH3:55])[CH2:53][CH2:52][C:48]=4[N:49]=[CH:50][N:51]=3)[C:28]2=[CH:29][CH:30]=1)=[O:24].CC(O)C>C1COCC1.O>[F:8][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=1)[C:23]([C:25]1[CH:26]=[C:27]2[C:33]3([CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)[CH2:32][N:31]([C:46]3[C:47]4[C@H:54]([CH3:55])[CH2:53][CH2:52][C:48]=4[N:49]=[CH:50][N:51]=3)[C:28]2=[CH:29][CH:30]=1)=[O:24]

Participants

8

Reactant 5

HCID 3776IsopropanolHCID 8058HexaneHCID 140821-Bromo-3-fluorobenzeneHCID 86651800HCID 86651800, compoundHCID 178418339Butyllithium

Product 1

HCID 68762560HCID 68762560, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-bromo-3-fluorobenzene (0.066 ml, 0.59 mmol) in THF (0.3 mL) was added dropwise n-BuLi in hexane (0.23 ml, 0.52 mmol) at about −78° C. under nitrogen. After being stirred at about −78° C. for about 20 minutes, a solution of (R)-tert-butyl 5-(methoxy(methyl)carbamoyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.050 g, 0.099 mmol) in THF (0.2 mL) was added dropwise to the reaction mixture at about −78° C. After 2 hours, i-PrOH (0.090 ml, 1.2 mmol) and water (2.0 mL) were added to the mixture, and the cold bath was removed. The mixture was stirred at about room temperature for about 20 minutes. The mixture was extracted with EtOAc. The combined organic layers were washed with water and brine, dried over MgSO4, and concentrated. The crude residue was purified by column chromatography (1-3% MeOH/DCM) to yield (R)-tert-butyl 5-(3-fluorobenzoyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.023 g, 43%). LCMS (APCI+) m/z 543.3 [M+H]+; Rt=4.49 min.

Workup

  1. waitAfter 2 hours
  2. customthe cold bath was removed
  3. stirringThe mixture was stirred at about room temperature for about 20 minutes
  4. extractionThe mixture was extracted with EtOAc
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe crude residue was purified by column chromatography (1-3% MeOH/DCM)

Sources & evidence

ORD record
ord-25994d968d8a4e808ee1b25b62df36c5
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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