Water → 4-Iodo-6-[3,5-bis(trifluoromethyl)benzyl]-6,7,8,9-tetrahydro-5H-10-oxa-1,6-diazabenzocyclooctene-5-one

HRID 1794997Notes

Reaction equation

HRID 1794997 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][N:7]([CH2:18][CH2:19][CH2:20][OH:21])[C:8](=[O:17])[C:9]1[C:14]([I:15])=[CH:13][CH:12]=[N:11][C:10]=1Cl.[H-].[Na+].O>O1CCCC1>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][N:7]1[CH2:18][CH2:19][CH2:20][O:21][C:10]2[N:11]=[CH:12][CH:13]=[C:14]([I:15])[C:9]=2[C:8]1=[O:17]

Participants

5

Reactant 3

HCID 962WaterHCID 24758Sodium hydrideHCID 11786369N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-(3-hydroxypropyl)-4-iodonicotinamide

Product 1

HCID 114780954-Iodo-6-[3,5-bis(trifluoromethyl)benzyl]-6,7,8,9-tetrahydro-5H-10-oxa-1,6-diazabenzocyclooctene-5-oneYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-[3,5-Bis(trifluoromethyl)benzyl]-2-chloro-N-(3-hydroxypropyl)-4-iodonicotinamide (compound of Reference Example 2; 6.86 g) was dissolved in tetrahydrofuran (60 mL). While the resulting solution was chilled on an ice bath, sodium hydride (581 mg, 60% oil suspension) was added, and the mixture was stirred for 30 minutes. The temperature of the mixture was then allowed to rise to room temperature, and the mixture was further stirred for 1 hour. While the reaction mixture was chilled on an ice bath, water was added, and then the resulting mixture was subjected to extraction with ethyl acetate. The resulting extract was washed with a saturated aqueous solution of sodium chloride, and was then dried on anhydrous sodium sulfate. The solvent was removed by distillation to obtain a residue, and then the residue was purified on a silica gel column chromatography (ethyl acetate:n-hexane=2:1) to obtain 5-[3,5-bis(trifluoromethyl)benzyl]-7-iodo6-oxo-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocine (2.69 g, 42%).

Workup

  1. temperatureWhile the resulting solution was chilled on an ice bath
  2. customto rise to room temperature
  3. stirringthe mixture was further stirred for 1 hour
  4. temperatureWhile the reaction mixture was chilled on an ice bath
  5. extractionthe resulting mixture was subjected to extraction with ethyl acetate
  6. extractionThe resulting extract
  7. washwas washed with a saturated aqueous solution of sodium chloride
  8. dry with materialwas then dried on anhydrous sodium sulfate
  9. customThe solvent was removed by distillation
  10. customto obtain a residue
  11. customthe residue was purified on a silica gel column chromatography (ethyl acetate:n-hexane=2:1)

Sources & evidence

ORD record
ord-6e48f609d59948aa806db32793d298dd
Source dataset
uspto-grants-2006_04
Patent number
US07026309B2

Reaction notes

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