Sodium Hydroxide → HCID 25060179, compound

HRID 641185Notes

Reaction equation

HRID 641185 reaction equation
[CH:1]12[CH2:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][C:3](=O)[CH2:2]2.[NH:10]1[CH2:15][CH2:14][C:13]2([O:20][C:19](=[O:21])[NH:18][C:17]3[CH:22]=[CH:23][CH:24]=[CH:25][C:16]2=3)[CH2:12][CH2:11]1.[BH4-].[Na+].[OH-].[Na+]>CO.CS(C)=O.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].ClCCl.C(COC)OC>[CH:1]12[CH2:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][CH:3]([N:10]1[CH2:11][CH2:12][C:13]3([O:20][C:19](=[O:21])[NH:18][C:17]4[CH:22]=[CH:23][CH:24]=[CH:25][C:16]3=4)[CH2:14][CH2:15]1)[CH2:2]2

Participants

10

Reactant 4

HCID 14798Sodium HydroxideHCID 139709Bicyclo[3.2.1]octan-3-oneHCID 4311764Sodium borohydrideHCID 13050639Spiro[3,1-benzoxazine-4,4'-piperidin]-2(1H)-one

Product 1

HCID 25060179HCID 25060179, compound

Reagents, catalysts & solvents 5

HCID 11026Titanium isopropoxideCatalystHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A scintillation vial was charged with bicyclo-[3.2.1]octan-3-one (iia) (31 mg, 0.25 mmol), spiro[4H-3,1-benzoxazine-4,4′-piperidin]-2(1H)-one (A4) (44 mg, 0.20 mmol), and anhydrous dimethoxyethane:dichloromethane (1.0 mL, 1:1 v/v). The mixture was treated with titanium tetraisopropoxide (171 mg, 0.60 mmol). The vial was flushed with nitrogen and stirred at room temperature for 60 hours. The reaction was then cooled in an ice water bath, quenched with methanol (1.0 mL) and treated with sodium borohydride (15 mg, 0.40 mmol). The reaction mixture was slowly warmed to room temperature, stirred for 1 hour, treated with 1.0 N NaOH (1.0 mL), diluted with methanol (2.0 mL), and stirred at room temperature for 15 min. The suspension obtained was centrifuged (3K rpm, 10 min), and the supernatant was filtered (Whatman 0.2 μm PTFE). The filtrate was concentrated under reduced pressure and the residue obtained dissolved in DMSO:methanol (1.5 mL, 1:1 v/v), filtered and subjected to reverse-phase HPLC purification [2-99% CH3CN gradient over 13 min with 0.1% TFA (aq), 35 mL/min, 1.0 mL injected] to provide 1′-(bicyclo[3.2.1]octan-3-yl)spiro[benzo[d][1,3]oxazine-4,4′-piperidin]-2(1H)-one (compound no. 67) as a TFA salt. LC/MS m/z 327.2 [M+H]+, retention time 1.80 min (RP-C18, 10-99% CH3CN/0.05% TFA).

Workup

  1. customThe vial was flushed with nitrogen
  2. temperatureThe reaction was then cooled in an ice water bath
  3. customquenched with methanol (1.0 mL)
  4. temperatureThe reaction mixture was slowly warmed to room temperature
  5. stirringstirred for 1 hour
  6. stirringstirred at room temperature for 15 min
  7. customThe suspension obtained
  8. filtrationthe supernatant was filtered (Whatman 0.2 μm PTFE)
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customthe residue obtained
  11. filtrationmethanol (1.5 mL, 1:1 v/v), filtered
  12. customsubjected to reverse-phase HPLC purification [2-99% CH3CN gradient over 13 min with 0.1% TFA (aq), 35 mL/min, 1.0 mL injected]

Sources & evidence

ORD record
ord-664b58822528486eb227cdb56f25ceec
Source dataset
uspto-grants-2010_04
Patent number
US07696201B2

Reaction notes

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