Phenol → HCID 117952138, compound

HRID 1499218Notes

Reaction equation

HRID 1499218 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C@H:9]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[N:21]2[CH:25]=[CH:24][C:23]([CH3:26])=[N:22]2)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([N:27]2[CH2:51][CH2:50][C:30]3([CH2:34][N:33]([C:35]([O:37][CH2:38][C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[O:36])[CH:32]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:31]3)[CH2:29][CH2:28]2)[N:3]=1.[C:52]1([OH:58])[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([C@@H:9]([O:8][C:6]2[CH:7]=[C:2]([O:58][C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[N:3]=[C:4]([N:27]3[CH2:51][CH2:50][C:30]4([CH2:34][N:33]([C:35]([O:37][CH2:38][C:39]5[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=5)=[O:36])[CH:32]([C:45]([O:47][CH2:48][CH3:49])=[O:46])[CH2:31]4)[CH2:29][CH2:28]3)[N:5]=2)[C:10]([F:12])([F:11])[F:13])=[C:15]([N:21]2[CH:25]=[CH:24][C:23]([CH3:26])=[N:22]2)[CH:16]=1

Participants

6

Reactant 3

HCID 996PhenolHCID 10796Cesium carbonateHCID 117951726HCID 117951726, compound

Product 1

HCID 117952138HCID 117952138, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2-benzyl 3-ethyl 8-(4-chloro-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (by-product from Step 3, Example 30a) (250 mg, 0.347 mmol) in 1,4-dioxane (9.0 mL) was added phenol (1.00 g, 10.6 mmol) and Cs2CO3 (3.65 g, 11.2 mmol). The reaction was heated at 80° C. for 12 h, then cooled to RT diluted with water, and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification on a 12 g Isco RediSep silica cartridge (EtOAc/heptane) provided 2-benzyl 3-ethyl 8-(4-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-6-phenoxypyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as an off-white solid.

Workup

  1. temperaturecooled to RT
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification on a 12 g Isco RediSep silica cartridge (EtOAc/heptane)

Sources & evidence

ORD record
ord-0b83d36a2c734c89bb892d1877b4fb8c
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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