Methanol → 2-(4-Bromo-2-methyl-phenyl)-9-oxa-2-aza-spiro[5.5]undecan-1-one

HRID 391187Notes

Reaction equation

C[O:2][C:3]([C:5]1([CH2:11][CH2:12][CH2:13][NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[CH3:22])[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=O.[H-].[Na+].CO.[Sn]>C1COCC1.C(Cl)Cl.C(OCC)(=O)C>[Br:21][C:18]1[CH:19]=[CH:20][C:15]([N:14]2[CH2:13][CH2:12][CH2:11][C:5]3([CH2:10][CH2:9][O:8][CH2:7][CH2:6]3)[C:3]2=[O:2])=[C:16]([CH3:22])[CH:17]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a clear solution of 4-[3-(4-bromo-2-methyl-phenylamino)-propyl]-tetrahydro-pyran-4-carboxylic acid methyl ester (0.85 g, 2.3 mmol) in THF (25 mL) was added NaH (60% in mineral oil, ˜100 mg) and the reaction temperature was raised to 50° C. (external) for 2 h. TLC (2.5% MeOH in DCM for SM, 5% MeOH in DCM for product) showed the reaction was complete. LC/MS detected the product peak. The reaction was cooled tin an ice-water bath, diluted with 25 mL of ethyl acetate, quenched with 10 mL of water. The two layers were separated. The aqueous layer was extracted with EtOAc (2×10 mL). The combined EtOAc extracts were washed with brine, and concentrated on rotavap to yield a crude product as a slightly yellow solid. This material was loaded onto a 25-g of silica gel column, eluted with DCM and 5% MeOH in DCM to get 0.81 g (95% yield) of the title compound as a white solid.

Workup

customquenched with 10 mL of water
customThe two layers were separated
extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
washThe combined EtOAc extracts were washed with brine
concentrationconcentrated on rotavap
customto yield a crude product as a slightly yellow solid
washeluted with DCM and 5% MeOH in DCM

Sources & evidence

ORD record: ord-6efa84151acc4759a6369b268d777d2c
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08383814B2

Reaction notes

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