1-Bromo-6-fluorohexane → (R/S)-(4-{2-[4-(6-fluoro-hexyloxy)-phenyl]-ethyl)-2-methyl-4,5-dihydro-oxazol-4-yl)-methanol

HRID 490063

Reaction equation

[OH:1][CH2:2][C:3]1([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[CH2:7][O:6][C:5]([CH3:8])=[N:4]1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][F:31].C([O-])(O)=O.[Na+]>CN(C=O)C.C(OCC)(=O)C>[F:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][O:17][C:14]1[CH:13]=[CH:12][C:11]([CH2:10][CH2:9][C:3]2([CH2:2][OH:1])[CH2:7][O:6][C:5]([CH3:8])=[N:4]2)=[CH:16][CH:15]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of (R/S)-4-[2-(4-hydroxymethyl-2-methyl-4,5-dihydro-oxazol-4-yl)-ethyl]-phenol (500 mg, 0.2.12 mmol) in dry DMF (8 ml) is added under inert atmosphere Cs2CO3 (901 mg, 2.76 mmol, 1.3 eq.) and 1-bromo-6-fluoro-hexane (464.1 mg, 2.55 mmol, 1.2 eq.). The reaction mixture is stirred under inert atmosphere at 85° C. overnight. A saturated solution of NaHCO3 (20 ml) and ethyl acetate (40 ml) are then added. The organic layer is separated and the aqueous phase is extracted with ethyl acetate (3×40 ml). The combined organic extracts are washed with brine and 1M HCl, dried over MgSO4, and evaporated to dryness. Purification by flash chromatography (cy Hexane/ethyl acetate(9/1) to (1/1) and (0/1)) affords (R/S)-(4-{2-[4-(6-fluoro-hexyloxy)-phenyl]-ethyl}-2-methyl-4,5-dihydro-oxazol-4-yl)-methanol as colorless oil.

Workup

customThe organic layer is separated
extractionthe aqueous phase is extracted with ethyl acetate (3×40 ml)
washThe combined organic extracts are washed with brine and 1M HCl
dry with materialdried over MgSO4
customevaporated to dryness
customPurification by flash chromatography (cy Hexane/ethyl acetate(9/1) to (1/1) and (0/1))

Sources & evidence

ORD record: ord-8bc27ecb4ab448359fd6bf48947efa65
Source dataset: uspto-grants-2009_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07528120B2

Linked notes

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