Phosphorus oxide (P4O10) → HCID 67429406, compound

HRID 410698Notes

Reaction equation

HRID 410698 reaction equation
C[C@:2]1([C:34]([OH:36])=[O:35])[CH2:7][CH2:6][C@:5](O)([C:8]2[S:9][C:10]([C:13]3[CH:18]=[C:17]([NH:19][C:20]4[N:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][N:21]=4)[CH:16]=[C:15]([CH3:30])[CH:14]=3)=[CH:11][N:12]=2)[CH2:4][C:3]1([CH3:33])[CH3:32].O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[C:51](=O)(O)[O-].[Na+]>>[CH3:32][C:3]1([CH3:33])[CH:4]=[C:5]([C:8]2[S:9][C:10]([C:13]3[CH:18]=[C:17]([NH:19][C:20]4[N:25]=[C:24]([C:26]([F:27])([F:29])[F:28])[CH:23]=[CH:22][N:21]=4)[CH:16]=[C:15]([CH3:30])[CH:14]=3)=[CH:11][N:12]=2)[CH2:6][CH2:7][CH:2]1[C:34]([O:36][CH3:51])=[O:35]

Participants

4

Reactant 3

HCID 14812Phosphorus oxide (P4O10)HCID 516892Sodium BicarbonateHCID 67433161HCID 67433161, compound

Product 1

HCID 67429406HCID 67429406, compoundYield 73%

Conditions

Temperature
65 °C

Procedure

A suspension of methyl (1S,4R)-4-hydroxy-2,2-dimethyl-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanecarboxylic acid (200 mg, 0.38 mmol) in phosphorous pentoxide (2.2 g, 15.4 mmol) was heated at 65° C. for 3 hours. The resulting mixture was cooled to room temperature, slowly poured into saturated aqueous sodium bicarbonate, and extracted with ethyl acetate (2×). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography (ethyl acetate/hexanes) afforded methyl 2,2-dimethyl-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohex-3-ene-1-carboxylate (141 mg, 0.28 mmol, 73% yield) as a colorless oil. MS ESI: [M+H]+ m/z 503.1.

Workup

  1. temperatureThe resulting mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (2×)
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification via silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0b94e0f376d545ad9c6d8b79c4879e9c
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

Loading…