Hydrochloric Acid → 6-(1-Hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-5-yloxy)-2-(2,2,2-trifluoro-ethoxy)-nicotinonitrile

HRID 1255729Notes

Reaction equation

Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[N:3]=1.[B:16]1([OH:26])[C:20]2[CH:21]=[CH:22][C:23]([OH:25])=[CH:24][C:19]=2[CH2:18][O:17]1.C([O-])([O-])=O.[Cs+].[Cs+].Cl>CN(C=O)C>[OH:26][B:16]1[C:20]2[CH:21]=[CH:22][C:23]([O:25][C:2]3[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[N:3]=3)=[CH:24][C:19]=2[CH2:18][O:17]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 6-chloro-2-(2,2,2-trifluoro-ethoxy)-nicotinonitrile (4, 1.26 g, 5.33 mmol) in DMF (anhydrous, 30 mL) were added 3H-benzo[c][1,2]oxaborole-1,5-diol (400 mg, 2.67 mmol) and Cs2CO3 (1.91 g, 5.87 mmol). The reaction was heated at 80° C. for 2 h by microwave. After the reaction cooled to room temperature, HCl (1 M, 20 mL) was added. The volatiles were removed in vacuo. Purification was accomplished by preparative HPLC, eluting with 5%-90% ACN/water gradient, to afford 380 mg (41% yield) of the title compound as a white solid.

Workup

temperatureAfter the reaction cooled to room temperature
customThe volatiles were removed in vacuo
customPurification
washeluting with 5%-90% ACN/water gradient

Sources & evidence

ORD record: ord-7ae6895e8d9b4c2d9c8bdbf947f450e1
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461135B2

Reaction notes

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