Potassium Carbonate → Trifluoroacetic acid

HRID 1255207Notes

Reaction equation

HRID 1255207 reaction equation
I[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([CH3:14])[CH:11]=[CH:10][C:9]=2[O:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C@H:23]3[CH2:28][CH2:27][C@H:26]([C:29]([F:32])([F:31])[F:30])[CH2:25][CH2:24]3)=[CH:19][CH:18]=2)[N:5]=[C:4]([N:33]2[C:37]([C:38]([F:41])([F:40])[F:39])=[C:36]([C:42]([O:44]CC)=[O:43])[CH:35]=[N:34]2)[CH:3]=1.[C:47]([O-:50])([O-])=[O:48].[K+].[K+].[CH3:53]B1OB(C)OB(C)O1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[C:47]([OH:50])([C:29]([F:32])([F:31])[F:30])=[O:48].[CH3:53][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([CH3:14])[CH:11]=[CH:10][C:9]=2[O:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C@H:23]3[CH2:24][CH2:25][C@H:26]([C:29]([F:30])([F:31])[F:32])[CH2:27][CH2:28]3)=[CH:19][CH:18]=2)[N:5]=[C:4]([N:33]2[C:37]([C:38]([F:41])([F:40])[F:39])=[C:36]([C:42]([OH:44])=[O:43])[CH:35]=[N:34]2)[CH:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 178469986HCID 178469986, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 178422638HCID 178422638, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of the title compound from Example 19 Step I (20 mg, 0.026 mmol) Pd(PPh3)4 (10.7 mg, 0.009 mmol), K2CO3 (11 mg, 0.08 mmol), trimethyl boroxine (11.6 mg, 0.09 mmol), and dioxane (0.5 mL) was heated in a microwave reactor at 140° C. for 1 h, cooled, diluted with hexanes and passed through a pad of silica gel eluted by dichloromethane. The solvent was removed in vacuo. Treatment with a mixture of 1,4-dioxane (0.1 mL), MeOH (0.1 mL) and 3 N NaOH (0.1 mL) at 50° C. for 15 min, followed by reverse phase HPLC using a YMC C-18 column (45 to 95% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 618.8 [M+H]+; 1H NMR (400 MHz, acetone-d6), δ 8.17 (s, 1H), 8.08 (s, 1H), 7.75 (d, J=2.1 Hz, 1H), 7.48 (s, 1H), 7.41 (d, J=8.1 Hz, 2H), 7.27 (d, J=8.1 Hz, 2H), 7.20 (dd, J=8.4 Hz, 2.1 Hz, 1H), 7.12 (d, J=8.4 Hz, 1H), 2.43 (s, 3H), 2.29 (s, 3H), 2.59 (m, 1H), 1.96 (m, 2H), 1.67-1.39 (m, 4H).

Workup

  1. temperaturecooled
  2. washeluted by dichloromethane
  3. customThe solvent was removed in vacuo
  4. additionTreatment with a mixture of 1,4-dioxane (0.1 mL), MeOH (0.1 mL) and 3 N NaOH (0.1 mL) at 50° C. for 15 min

Sources & evidence

ORD record
ord-168d2791f29e44b484f675d058ea9a6b
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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