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

HRID 12371

Reaction equation

HRID 12371 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]([CH:18]([NH2:27])[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)([OH:17])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:29][C:30](Cl)=[O:31].[Na+].[I-].[I-].CC(C)([O-])C>>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][C:14]2([O:17][CH2:29][C:30](=[O:31])[NH:27][CH:18]2[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 5238Sodium IodideHCID 6577Chloroacetyl chlorideHCID 30165Iodide IonHCID 45749132-Methylpropan-2-olateHCID 574580144-[1-Amino-2-(4-fluorophenyl)-ethyl]-4-hydroxypiperidine-1-carboxylic acid benzyl ester

Product 1

HCID 675274075-(4-Fluorobenzyl)-3-oxo-1-oxa-4,9-diaza-spiro[5.5]undecane-9-carboxylic acid benzyl esterYield 19%

Procedure

The title compound was prepared from aminoalcohol 103NLS28 (303 mg, 0.81 mmol) according to literature procedures (Clark et al., J. Med. Chem. 26:855-861 (1983)), by acylation of the amino function with chloroacetylchloride, followed by halogen exchange with NaI and ring closure of the iodide derivative in presence of tert-butoxide. Purification of the crude product by silica gel column chromatography, eluting with a stepwise gradient of 0-100% ethyl acetate in n-heptane, afforded the title compound (64 mg, 19% overall yield) as a colourless solid.

Workup

  1. customPurification of the crude product by silica gel column chromatography
  2. washeluting with a stepwise gradient of 0-100% ethyl acetate in n-heptane

Sources & evidence

ORD record
ord-4ff04c5e94c1429fb6e2c8b432ea5d8a
Source dataset
uspto-grants-2010_06
Patent number
US07727999B2

Linked notes

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