2-Fluoroethanol → HCID 24780661, compound

HRID 2241811Notes

Reaction equation

C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].Br[C:37]1[N:42]=[CH:41][C:40]([C:43]2[O:44][C:45]3[CH:51]=[C:50]([O:52][CH3:53])[CH:49]=[CH:48][C:46]=3[N:47]=2)=[CH:39][CH:38]=1.[F:54][CH2:55][CH2:56][OH:57]>CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1>[F:54][CH2:55][CH2:56][O:57][C:37]1[N:42]=[CH:41][C:40]([C:43]2[O:44][C:45]3[CH:51]=[C:50]([O:52][CH3:53])[CH:49]=[CH:48][C:46]=3[N:47]=2)=[CH:39][CH:38]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Toluene (1 mL) was added to Pd(OAc)2 (6.4 μmol), 2-(di-t-butylphosphino)-1,1′-binaphtyl (racemic, 8.0 μmol), Cs2CO3 (0.24 mmol) and 2-(6-bromopyridin-3-yl)-6-methoxy-1,3-benzoxazole under Ar. 2-Fluoroethanol (0.16 mmol) was added and the reaction was stirred 1 h at 120° C. Additional Pd(OAc)2 (8.0 μmol), 2-(di-t-butylphosphino)-1,1′-binaphtyl (racemic, 8.0 μmol) and 2-fluoroethanol (0.16 mmol) was added and the mixture was again stirred 1 h at 120° C. The reaction mixture was cooled to r.t., diluted with EtOAc, filtered through celite and concentrated. The crude product was subjected to reverse phase HPLC to afford the title compound as an off white solid (10.1 mg). 1H NMR (400 MHz, Chloroform-d) δ ppm 8.95 (d, 1H) 8.36 (dd, 1H) 7.62 (d, 1H) 7.12 (d, 1H) 6.91-6.99 (m, 2H) 4.82-4.88 (m, 1H) 4.69-4.76 (m, 2H) 4.61-4.66 (m, 1H) 3.89 (s, 3 H); MS m/z (M+H) 289.

Workup

waitthe mixture was again stirred 1 h at 120° C
temperatureThe reaction mixture was cooled to r.t.
filtrationfiltered through celite
concentrationconcentrated

Sources & evidence

ORD record: ord-72232ee2ace04f9686cca6e6c145f8ea
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07670591B2

Reaction notes

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