Methanol → Methyl 5-(1,1,1-trifluoro-2-hydroxypropan-2-yl)pyridine-3-carboxylate

HRID 1048941Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:8]([OH:14])([CH3:13])[C:9]([F:12])([F:11])[F:10])[CH:5]=[N:6][CH:7]=1.CC1(C)C2[C:37](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:36][C:18]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C[OH:58].C(N(CC)CC)C>C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:10][C:9]([F:12])([F:11])[C:8]([C:4]1[CH:3]=[C:2]([C:18]([O:36][CH3:37])=[O:58])[CH:7]=[N:6][CH:5]=1)([OH:14])[CH3:13]

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of the title compound from Step A (0.170 g, 0.628 mmol), Pd(OAc)2 (2.8 mg, 0.013 mmol), Xantphos (0.015 g, 0.025 mmol), methanol (0.254 mL, 6.28 mmol), and triethylamine (8.96 mL, 1.25 mmol) was stirred under an atmosphere of carbon monoxide at 70° C. overnight. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, filtered through Celite using ethyl acetate and concentrated under reduced pressure. Purification by column chromatography on silica gel (30% ethyl acetate in hexanes) provided the title compound: LCMS m/z 250.02 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.22 (s, 1 H), 9.00 (s, 1 H), 8.52 (s, 1 H), 3.98 (s, 3 H), 2.94 (br s, 1 H), 1.86 (s, 3 H).

Workup

temperatureThe reaction mixture was cooled to room temperature
filtrationfiltered through Celite
concentrationconcentrated under reduced pressure
customPurification by column chromatography on silica gel (30% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-f19040f2bda1416dab1f30535f6a2dde
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382226B2

Reaction notes

Loading…