Triethylamine → 2-(2,6-difluorophenyl)-4-(4-chlorophenyl)-5,6-dihydro-4H-1,3-oxazine

HRID 1276212Notes

Reaction equation

HRID 1276212 reaction equation
CS(Cl)(=O)=O.[F:6][C:7]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:8]=1[C:9]([NH:11][CH:12]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)[CH2:13][CH2:14][OH:15])=O.C(N(CC)CC)C>O1CCCC1>[F:6][C:7]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:8]=1[C:9]1[O:15][CH2:14][CH2:13][CH:12]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[N:11]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 15790732N-(2,6-difluorobenzoyl)-3-amino-3-(4-chlorophenyl) 1-propanol

Product 1

HCID 157907332-(2,6-difluorophenyl)-4-(4-chlorophenyl)-5,6-dihydro-4H-1,3-oxazineYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of 1.74 g (15.2 mmol) of methanesulfonyl chloride and 10 ml of tetrahydrofuran is added dropwise to a mixture of 4.5 g (13.8 mmol) of N-(2,6-difluorobenzoyl)-3-amino-3-(4-chlorophenyl)-1-propanol, 1.54 g (15.2 mmol) of triethylamine and 50 ml of tetrahydrofuran, while cooling with ice and stirring. The mixture is stirred at room temperature for 2 hours and filtered, and the filtrate is concentrated in vacuo. The residue is taken up in 50 ml of methanol, 2 g of potassium hydroxide are added and the mixture is stirred at 70° C. for 30 minutes. After customary working up, the crude product is purified by column chromatography on silica gel using the mobile phase n-hexane/ethyl acetate 8/2. 3.1 g (72.9%) of 2-(2,6-difluorophenyl)-4-(4-chlorophenyl)-5,6-dihydro-(4H)1,3-oxazine are obtained as a colorless oil.

Workup

  1. temperaturewhile cooling with ice
  2. stirringThe mixture is stirred at room temperature for 2 hours
  3. filtrationfiltered
  4. concentrationthe filtrate is concentrated in vacuo
  5. addition2 g of potassium hydroxide are added
  6. stirringthe mixture is stirred at 70° C. for 30 minutes
  7. customthe crude product is purified by column chromatography on silica gel using the mobile phase n-hexane/ethyl acetate 8/2

Sources & evidence

ORD record
ord-68b8b8bda201497097e3344b43334aa8
Source dataset
uspto-grants-2000_12
Patent number
US06166010

Reaction notes

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