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

HRID 529067Notes

Reaction equation

HRID 529067 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]3)[CH2:9][N:8]([C:23]3[C:24]4[C@H:31]([CH3:32])[CH2:30][C@@H:29](O)[C:25]=4[N:26]=[CH:27][N:28]=3)[C:5]2=[CH:6][CH:7]=1.CCN(S(F)(F)[F:40])CC>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]3)[CH2:9][N:8]([C:23]3[C:24]4[C@H:31]([CH3:32])[CH2:30][C@H:29]([F:40])[C:25]=4[N:26]=[CH:27][N:28]=3)[C:5]2=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 68759438tert-butyl 5-chloro-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylate

Product 1

HCID 69810671tert-butyl 5-chloro-1-((5R,7S)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-carboxylateYield 40.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

A solution of tert-butyl 5-chloro-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.010 g, 0.021 mmol) in DCM (0.3 mL) was cooled to about −20° C. The solution was treated with DAST (0.0084 ml, 0.064 mmol) and stirred at about −20° C. for 1.5 hours. The reaction was quenched with ice then warmed to ambient temperature. The mixture was diluted with saturated aqueous NH4Cl solution. The organic layer was separated. The aqueous phase was extracted with DCM. The combined organics were dried over MgSO4, filtered and concentrated. The crude residue was purified by column chromatography (30-50% EtOAc/Hexane) to yield tert-butyl 5-chloro-1-((5R,7S)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.004 g, 40%). LCMS (APCI+) m/z 473, 475 [M+H]+; Rt=3.98 min.

Workup

  1. customThe reaction was quenched with ice
  2. temperaturethen warmed to ambient temperature
  3. additionThe mixture was diluted with saturated aqueous NH4Cl solution
  4. customThe organic layer was separated
  5. extractionThe aqueous phase was extracted with DCM
  6. dry with materialThe combined organics were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by column chromatography (30-50% EtOAc/Hexane)

Sources & evidence

ORD record
ord-85814a9c5791421089b14a21682c0ed6
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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