Hydrochloric Acid → HCID 68735863, compound

HRID 529079Notes

Reaction equation

HRID 529079 reaction equation
C(O)(C(F)(F)F)=O.[BH4-].[Na+].[F:10][C:11]1[CH:12]=[C:13]([CH:17](O)[C:18]2[CH:19]=[C:20]3[C:26]4([CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]4)[CH2:25][N:24]([C:39]4[C:40]5[C@H:47]([CH3:48])[CH2:46][CH2:45][C:41]=5[N:42]=[CH:43][N:44]=4)[C:21]3=[CH:22][CH:23]=2)[CH:14]=[CH:15][CH:16]=1.[OH-].[Na+].[ClH:52]>C(Cl)Cl.O.CCOCC>[ClH:52].[ClH:52].[F:10][C:11]1[CH:12]=[C:13]([CH:14]=[CH:15][CH:16]=1)[CH2:17][C:18]1[CH:19]=[C:20]2[C:26]3([CH2:27][CH2:28][NH:29][CH2:30][CH2:31]3)[CH2:25][N:24]([C:39]3[C:40]4[C@H:47]([CH3:48])[CH2:46][CH2:45][C:41]=4[N:42]=[CH:43][N:44]=3)[C:21]2=[CH:22][CH:23]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 4311764Sodium borohydride2×HCID 69812189HCID 69812189, compound

Product 1

HCID 68735863HCID 68735863, compoundYield 6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A flask charged with TFA (0.294 ml, 3.82 mmol) was cooled to about 0° C. and treated with NaBH4 (0.0133 g, 0.353 mmol) in small portions. The mixture was stirred for 1 hour. A solution of tert-butyl 5-((3-fluorophenyl)(hydroxy)methyl)-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (0.032 g, 0.0588 mmol) in DCM (0.18 mL) was added slowly over about 15 minutes. The mixture was allowed to warm to about room temperature and stirred overnight. An additional 3 equivalents of NaBH4 was added the reaction was stirred at about room temperature overnight. The reaction was diluted with water, basified with 2N NaOH, and extracted with EtOAc. The combined organics were washed with water, dried over MgSO4, filtered, and concentrated. The crude residue was purified by column chromatography (4% 7 N ammonia in MeOH/DCM) to yield the free base, which was taken up in DCM and acidified with 2N HCl in Et2O. Removal of the solvents afforded ((R)-5-(3-fluorobenzyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]dihydrochloride (0.001 g, 6%). LCMS (APCI+) m/z 429.4 [M+H]+; Rt=3.15 min.

Workup

  1. temperatureto warm to about room temperature
  2. stirringstirred overnight
  3. stirringwas stirred at about room temperature overnight
  4. extractionextracted with EtOAc
  5. washThe combined organics were washed with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by column chromatography (4% 7 N ammonia in MeOH/DCM)
  10. customto yield the free base, which
  11. customRemoval of the solvents

Sources & evidence

ORD record
ord-c315e2b54f0049f9b36c00e184e9f184
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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