Acetic Acid → [4-[[4,5-Dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzoyl]amino]-2-oxo-1-pyridyl]methyl dihydrogen phosphate

HRID 1752994Notes

Reaction equation

HRID 1752994 reaction equation
[P:1]([O:13][CH2:14][N:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:41])[C:23]2[CH:28]=[C:27]([Cl:29])[C:26]([Cl:30])=[CH:25][C:24]=2[O:31][C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[O:39][CH3:40])=[CH:17][C:16]1=[O:42])([O:8]C(C)(C)C)([O:3]C(C)(C)C)=[O:2].CC(O)=O>CC#N.O>[P:1]([OH:3])([OH:8])([O:13][CH2:14][N:15]1[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:41])[C:23]2[CH:28]=[C:27]([Cl:29])[C:26]([Cl:30])=[CH:25][C:24]=2[O:31][C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][C:33]=2[O:39][CH3:40])=[CH:17][C:16]1=[O:42])=[O:2]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 118148564Di-tert-butyl [4-[[4,5-dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzoyl]amino]-2-oxo-1-pyridyl]methyl phosphate

Product 1

HCID 118126595[4-[[4,5-Dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzoyl]amino]-2-oxo-1-pyridyl]methyl dihydrogen phosphateYield 54.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of di-tert-butyl [4-[[4,5-dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzoyl]amino]-2-oxo-1-pyridyl]methyl phosphate (40 mg, 0.06197 mmol) in CH3CN (800.0 μL), water (800.0 μL) and AcOH (800 μL, 14.07 mmol) was heated at 90° C. for 15 min then evaporated and co-evaporated with CH3CN (3×). The material was triturated with CH3CN, filtered, washed with CH3CN and desiccated to give [4-[[4,5-dichloro-2-(4-fluoro-2-methoxy-phenoxy)benzoyl]amino]-2-oxo-1-pyridyl]methyl dihydrogen phosphate (1) (19 mg, 0.03385 mmol, 54.6%) as a white solid. ESI-MS m/z calc. 532.00055, found 533.3 (M+1)+; Retention time: 1.5 minutes. 1H NMR (400 MHz, DMSO-d6) δ 10.58 (s, 1H), 7.91 (s, 1H), 7.62 (d, J=7.6 Hz, 1H), 7.27 (dd, J=8.9, 5.8 Hz, 1H), 7.13 (dd, J=10.7, 3.0 Hz, 1H), 6.90 (d, J=2.3 Hz, 1H), 6.86 (s, 1H), 6.86-6.81 (m, 1H), 6.44 (dd, J=7.6, 2.4 Hz, 1H), 5.52 (d, J=9.7 Hz, 2H), 3.76 (s, 3H) ppm. 31P NMR (162 MHz, DMSO-d6-85% H3PO4 aq. as internal standard—0 ppm) δ −2.12 (t, J=9.4 Hz) ppm.

Workup

  1. customthen evaporated
  2. customThe material was triturated with CH3CN
  3. filtrationfiltered
  4. washwashed with CH3CN

Sources & evidence

ORD record
ord-7b2fc78a4f8c4ef39252b35b103f2541
Source dataset
uspto-grants-2015_10
Patent number
US09163042B2

Reaction notes

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