2,2,2-Trifluoroethanol → Trifluoroacetic acid

HRID 1948098Notes

Reaction equation

HRID 1948098 reaction equation
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:27]=[CH:26][C:16]([CH2:17][P:18](=[O:25])([O:22][CH2:23][CH3:24])[O:19][CH2:20][CH3:21])=[CH:15][C:14]=2[O:28][CH3:29])[N:3]=1.[NH2:30][C:31]1[CH:32]=[CH:33][C:34]([N:42]2[CH2:47][CH2:46][NH:45][CH:44]([C:48]([O:50]C)=[O:49])[CH2:43]2)=[C:35]2[C:39]=1[C:38](=[O:40])[N:37]([CH3:41])[CH2:36]2.[F:52][C:53]([F:58])([F:57])[C:54]([OH:56])=[O:55].C(O)C(F)(F)F.O.[OH-].[Li+]>O.CO.C1COCC1>[CH2:20]([O:19][P:18]([CH2:17][C:16]1[CH:26]=[CH:27][C:13]([NH:12][C:4]2[N:3]=[C:2]([NH:30][C:31]3[CH:32]=[CH:33][C:34]([N:42]4[CH2:47][CH2:46][NH:45][CH:44]([C:48]([OH:50])=[O:49])[CH2:43]4)=[C:35]4[C:39]=3[C:38](=[O:40])[N:37]([CH3:41])[CH2:36]4)[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=2)=[C:14]([O:28][CH3:29])[CH:15]=1)([O:22][CH2:23][CH3:24])=[O:25])[CH3:21].[F:52][C:53]([F:58])([F:57])[C:54]([OH:56])=[O:55]

Participants

10

Reactant 5

HCID 64092,2,2-TrifluoroethanolHCID 6422Trifluoroacetic acidHCID 168937Lithium hydroxide, monohydrateHCID 67253563HCID 67253563, compound2×HCID 86654002Diethyl (4-{[4-chloro-5-(trifluoromethyl) pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

Product 2

HCID 6422Trifluoroacetic acidYield 48.2%HCID 58293019HCID 58293019, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
105 °C

Procedure

Diethyl (4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (18 mg, 0.039 mmol), methyl 4-(7-amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)piperazine-2-carboxylate (Compound 287A, 6.0 mg, 0.020 mmol), trifluoroacetic acid (4.6 μL, 0.060 mmol) and 0.5 mL trifluoroethanol were mixed. The mixture was heated in microwave 105° C. for 30 minutes. Solvent was evaporated. To the crude solid was added, 0.1 mL THF, 0.1 mL methanol, 0.1 mL water and lithium hydroxide monohydrate (8.3 mg, 0.20 mmol). The mixture was stirred at room temperature overnight. The crude material was purified by MDP to obtain the title compound as a trifluoroacetic acid salt (1.1 mg, 7.9% yield). 1H NMR (400 MHz, methanol-d4) δ=1.28 (t, J=7.3 Hz, 6H), 3.18 (s, 3H), 3.21-3.24 (m, 1 H), 3.33 (d, J=21.7 Hz, 2H), 3.37-3.43 (m, 2H), 3.45-3.51 (m, 1H), 3.55-3.61 (m, 2H), 3.90 (s, 3H), 4.06-4.11 (m, 4H), 4.32-4.39 (m, 1H), 4.44-4.59 (m, 2H), 6.99 (d, J=7.8 Hz, 1H), 7.09 (s, 1H), 7.25 (d, J=8.8 Hz, 1H), 7.75 (d, J=8.3 Hz, 1H), 8.35 (s, 1H), 8.49 (br. s., 1H). MS (ES+): m/z 708.26 (100) [MH+]; HPLC: tR=0.77 min (UPLC, purity).

Workup

  1. customSolvent was evaporated
  2. additionTo the crude solid was added
  3. customThe crude material was purified by MDP

Sources & evidence

ORD record
ord-c6ad0a84c65a4aa7a28bf5a3c182ee0c
Source dataset
uspto-grants-2013_03
Patent number
US08399433B2

Reaction notes

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