Boron tribromide → (R)-3-(N,N-Dicyclobutylamino)-8-fluoro-5-hydroxy-3,4-dihydro-2H-1-benzopyran

HRID 52270Notes

Reaction equation

Cl.[F:2][C:3]1[C:12]2[O:11][CH2:10][C@H:9]([N:13]([CH:18]3[CH2:21][CH2:20][CH2:19]3)[CH:14]3[CH2:17][CH2:16][CH2:15]3)[CH2:8][C:7]=2[C:6]([O:22]C)=[CH:5][CH:4]=1.B(Br)(Br)Br>C(Cl)Cl>[F:2][C:3]1[C:12]2[O:11][CH2:10][C@H:9]([N:13]([CH:14]3[CH2:17][CH2:16][CH2:15]3)[CH:18]3[CH2:19][CH2:20][CH2:21]3)[CH2:8][C:7]=2[C:6]([OH:22])=[CH:5][CH:4]=1

Participants

Conditions

Temperature: -40 °C

Procedure

(R)-8-Fluoro-3-(N,N-dicyclobutylamino)-5-methoxy-3,4-dihydro-2H-1-benzopyran hydrochloride (0.77 g, 2.26 mmol) was dissolved in anhydrous CH2Cl2 (20 mL) and cooled to -40° C. To the solution was BBr3 (0.54 mL, 5.7 mmol), dissolved in anhydrous CH2Cl2 (3 mL), added dropwise. The cooling-bath was removed and after 2 h at room temperature the reaction was completed. The reaction was poured out onto an ice/2M NH3 solution and the mixture was extracted, twice, with (MgSO4), filtered, and the solvent removed in vacuo to diethyl ether. The combined ether portions were dried give the crude residue. Chromatography on silica (eluent: 50% ethyl acetate/hexane) gave 0.58 g (89% yield) of the title compound as a white solid. Mp: 170°-2° C. [α]21D =-114.4° (C=0.1; CHCl3) GC-MS (70 eV) M=291 (2%).

Workup

additionadded dropwise
customThe cooling-bath was removed and after 2 h at room temperature the reaction
additionThe reaction was poured out onto an ice/2M NH3 solution
extractionthe mixture was extracted
filtrationtwice, with (MgSO4), filtered
customthe solvent removed in vacuo to diethyl ether
dry with materialThe combined ether portions were dried
customgive the crude residue

Sources & evidence

ORD record: ord-340fe5526c274f7aa73eec05c2fe8b8f
Source dataset: uspto-grants-1997_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05616610

Reaction notes

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