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

HRID 749273Notes

Reaction equation

HRID 749273 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)([O-])[O-].[K+].[K+].[CH2:45](Br)[CH3:46].[ClH:48]>CN(C=O)C.C(OCC)C>[ClH:48].[F:36][C:33]1[CH:32]=[CH:31][C:30]([CH2:29][CH:12]2[C:11]3([CH2:37][CH2:38][N:8]([CH2:45][CH3:46])[CH2:9][CH2:10]3)[O:15][C:14](=[O:16])[N:13]2[CH2:17][C:18]2[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH:26]([CH3:28])[CH3:27])=[CH:22][CH:23]=2)=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 6332Ethyl BromideHCID 11430Potassium CarbonateHCID 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 1317269734-(4-Fluorobenzyl)-3-(4-isobutoxybenzyl)-8-ethyl-1-oxa-3 8-diaza-spiro[4.5]decan-2-one, hydrochloride

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

69NLS77 (190 mg, 0.45 mmol) was N-BOC deprotected as described in the preparation of 69NLS79-II and dissolved in DMF (3 mL). Potassium carbonate (250 mg, 1.80 mmol) was added, followed by ethylbromide (50 μL, 0.45 mmol)) and the mixture stirred overnight at rt. Workup was carried out as for 69NLS79-II. The residue was purified by silica gel column chromatography, eluting with a stepwise gradient of 0-6% methanol in dichloromethane, followed by repurification of the compound by acidic ion-exchange SPE cartridge, to give 38-PH20 (77 mg, 38%) as a colourless oil. The compound was converted to its hydrochloride form by treatment with 2M HCl in diethylether as described above, giving the salt as a colorless powder.

Workup

  1. customas described in the preparation of 69NLS79-II and
  2. customThe residue was purified by silica gel column chromatography
  3. washeluting with a stepwise gradient of 0-6% methanol in dichloromethane
  4. customfollowed by repurification of the compound by acidic ion-exchange SPE cartridge
  5. customto give 38-PH20 (77 mg, 38%) as a colourless oil

Sources & evidence

ORD record
ord-aa5ca4400bdd4e85a11db0f8ffafb822
Source dataset
uspto-grants-2008_07
Patent number
US07402590B2

Reaction notes

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