Methanol → methyl 7-hydroxy-8-methyl-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 854869Notes

Reaction equation

C[O:2][C:3]1[C:12]([CH3:13])=[C:11]2[C:6]([CH:7]=[C:8]([C:18]([O:20][CH2:21]C)=[O:19])[CH:9]([C:14]([F:17])([F:16])[F:15])[O:10]2)=[CH:5][CH:4]=1.B(Br)(Br)Br.CO>C(Cl)Cl>[OH:2][C:3]1[C:12]([CH3:13])=[C:11]2[C:6]([CH:7]=[C:8]([C:18]([O:20][CH3:21])=[O:19])[CH:9]([C:14]([F:17])([F:15])[F:16])[O:10]2)=[CH:5][CH:4]=1

Participants

Conditions

Temperature: -78 °C

Procedure

The ethyl 7-methoxy-8-methyl-2-(trifluoromethyl)-2H-chromene-3-carboxylate from Example 3a, Step 2 (3.0 g, 9.49 mmole) was dissolved in methylene chloride (120 mL). The solution was chilled to −78° C. and BBr3 (94.9 mL, 1 M solution in CH2Cl2) was added slowly to the above solution. The reaction was slowly warmed to room temperature and stirred overnight. The reaction was cooled to −78° C. and MeOH (30 mL) added in. After the solution was stirred at room temperature for 2 h, the reaction was evaporated to dryness to give a brownish solid having ca.90% purity. The crude product was further purified by passing through a silica plug to give a yellow solid (2.7 g, 80%): LCMS m/z 311.05 (M+Na). 1H NMR (acetone-d6/400 MHz) 9.11 (s, 1H), 7.75 (s, 1H), 7.11(d, 1H, J=8.4 Hz), 6.59 (d, 1H, J=8.4 Hz), 5.78 (q, 1H, J=6 Hz), 3.79 (s, 3H), 2.09(s, 3H).

Workup

temperatureThe reaction was slowly warmed to room temperature
temperatureThe reaction was cooled to −78° C.
stirringAfter the solution was stirred at room temperature for 2 h
customthe reaction was evaporated to dryness
customto give a brownish solid
customThe crude product was further purified

Sources & evidence

ORD record: ord-0caab39bacb64af7b17038cb09f22ba5
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07259266B2

Reaction notes

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