5-(4-Fluorobenzyl)-4-(4-isobutoxybenzyl)-3-oxo-1-oxa-4,9-diaza-spiro[5.5]undecane-9-carboxylic acid benzyl ester → 5-(4-Fluorobenzyl)-4-(4-isobutoxybenzyl)-1-oxa-4,9-diaza-spiro[5.5]undecan-3-one

HRID 1072559Notes

Reaction equation

HRID 1072559 reaction equation
C(OC([N:11]1[CH2:42][CH2:41][C:14]2([O:19][CH2:18][C:17](=[O:20])[N:16]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH:30]([CH3:32])[CH3:31])=[CH:24][CH:23]=3)[CH:15]2[CH2:33][C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[CH2:13][CH2:12]1)=O)C1C=CC=CC=1>C(O)C.[Pd]>[F:40][C:37]1[CH:36]=[CH:35][C:34]([CH2:33][CH:15]2[C:14]3([CH2:13][CH2:12][NH:11][CH2:42][CH2:41]3)[O:19][CH2:18][C:17](=[O:20])[N:16]2[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH:30]([CH3:31])[CH3:32])=[CH:24][CH:23]=2)=[CH:39][CH:38]=1

Participants

4

Reactant 1

HCID 574580155-(4-Fluorobenzyl)-4-(4-isobutoxybenzyl)-3-oxo-1-oxa-4,9-diaza-spiro[5.5]undecane-9-carboxylic acid benzyl ester

Product 1

HCID 223867585-(4-Fluorobenzyl)-4-(4-isobutoxybenzyl)-1-oxa-4,9-diaza-spiro[5.5]undecan-3-one

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

The spirocycle 103NLS33 (62 mg, 0.107 mmol) in ethanol (5 mL) was N-CBz-deprotected by hydrogenation in presence of Pd/C (10%, 40 mg) under H2-balloon pressure. The catalyst was filtered off and the filtrate evaporated under reduced pressure to give crude 5-(4-fluorobenzyl)-4-(4-isobutoxybenzyl)-1-oxa-4,9-diaza-spiro[5.5]undecan-3-one. The residue was dissolved in methanol (3 mL), formaldehyde (37% in water, 0.017 mL) added, followed by the addition of acetic acid (0.03 mL) and sodium cyanoborohydride (60 mg, 0.95 mmol). The solution was stirred at rt for 5 h, then water was added and the mixture basified with 2 N aq. NaOH solution. The mixture was extracted three times with dichloromethane, the combined organic layers washed with sat. ammonium chloride solution and brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by column chromatography on silica gel, eluting with a stepwise gradient of 0-7% methanol in dichloromethane, giving 103NLS35B (43 mg, 88% over both steps) as a colorless oil. The compound was converted to its HCl form by treatment with 2 M HCl in diethylether as described above for 69NLS75, affording the salt as a colorless powder.

Workup

  1. filtrationThe catalyst was filtered off
  2. customthe filtrate evaporated under reduced pressure

Sources & evidence

ORD record
ord-298c5aecffb54f618980a2f616da54cf
Source dataset
uspto-grants-2005_06
Patent number
US06911452B2

Reaction notes

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