Hydrochloric Acid → 8-(2-[1,3]Dioxolan-2-yl-ethyl)-4-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3.8-diaza-spiro[4.5]decan-2-one, hydrochloride

HRID 749271Notes

Reaction equation

HRID 749271 reaction equation
C(OC([N:8]1[CH2:38][CH2:37][C:11]2([O:15][C:14](=[O:16])[N:13]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH:26]([CH3:28])[CH3:27])=[CH:20][CH:19]=3)[CH:12]2[CH2:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(=O)([O-])[O-].[K+].[K+].Br[CH2:53][CH2:54][CH:55]1[O:59][CH2:58][CH2:57][O:56]1.[I-].[Na+].[ClH:62]>C(OCC)C>[ClH:62].[O:56]1[CH2:57][CH2:58][O:59][CH:55]1[CH2:54][CH2:53][N:8]1[CH2:9][CH2:10][C:11]2([O:15][C:14](=[O:16])[N:13]([CH2:17][C:18]3[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH:26]([CH3:27])[CH3:28])=[CH:22][CH:23]=3)[CH:12]2[CH2:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[CH2:37][CH2:38]1

Participants

8

Reactant 6

HCID 313Hydrochloric Acid2×HCID 5238Sodium IodideHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 877762-(2-Bromoethyl)-1,3-dioxolaneHCID 574260414-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-2-oxo-1-oxa-3,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester

Product 1

HCID 1317269728-(2-[1,3]Dioxolan-2-yl-ethyl)-4-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-oxa-3.8-diaza-spiro[4.5]decan-2-one, hydrochloride

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
50 °C

Procedure

69NLS77 (300 mg, 0.57 mmol) was N-BOC deprotected by treatment with a solution of TFA (2 mL) in dichlornethane (2 mL) at rt for 1.5 h. The solvent was removed in vacuo, the residue coevaporated twice with acetonitrile and redissolved in the same solvent (10 mL). Potassium carbonate (110 mg, 0.80 mmol) and 2-(2-bromoethyl) 1,3-dioxolane (80 μL, 0.68 mmol) were added, followed by sodium iodide (102 mg, 0.68 mmol) and the mixture stirred for 3 days at 50° C. Partitioning of the mixture between water and dichloromethane, extraction of the aqueous layer twice with dichloromethane, drying of the combined organic layers over Na2SO4, filtering and evaporation of the solvent gave crude 69NLS79-II. The residue was purified by silica gel column chromatography, eluting with a stepwise gradient of 0-4% methanol in dichloromethane, affording 69NLS79-II (127 mg, 0.24 mmol) as a colorless oil. The compound was converted to its HCl form by treatment with 2M HCl in diethylether as described above for 69NLS75, giving the salt as a colorless powder.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionredissolved in the same solvent (10 mL)
  3. customPartitioning of the mixture between water and dichloromethane, extraction of the aqueous layer twice with dichloromethane
  4. dry with materialdrying of the combined organic layers over Na2SO4
  5. filtrationfiltering
  6. customevaporation of the solvent
  7. customgave crude 69NLS79-II
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with a stepwise gradient of 0-4% methanol in dichloromethane
  10. customaffording 69NLS79-II (127 mg, 0.24 mmol) as a colorless oil

Sources & evidence

ORD record
ord-02b7dec5638441c486bdd9525911ddc8
Source dataset
uspto-grants-2008_07
Patent number
US07402590B2

Reaction notes

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