Hydrochloric Acid → HCID 86712808, compound

HRID 876374Notes

Reaction equation

HRID 876374 reaction equation
COC1C=CC(C(C2C=CC(OC)=CC=2)(C2C=CC=CC=2)[NH:10][C:11]2[O:12][CH2:13][CH2:14][C@@:15]([CH:38]([F:40])[F:39])([C:17]3[CH:22]=[C:21]([N:23]=C(C4C=CC=CC=4)C4C=CC=CC=4)[CH:20]=[CH:19][C:18]=3[F:37])[N:16]=2)=CC=1.FC(F)(F)C(O)=O.Cl.C([O-])([O-])=O.[Na+].[Na+]>ClCCl.O1CCOCC1>[NH2:23][C:21]1[CH:20]=[CH:19][C:18]([F:37])=[C:17]([C@:15]2([CH:38]([F:39])[F:40])[CH2:14][CH2:13][O:12][C:11]([NH2:10])=[N:16]2)[CH:22]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 86712807HCID 86712807, compound

Product 1

HCID 86712808HCID 86712808, compoundYield 43.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of (S)—N-(bis(4-methoxyphenyl)(phenyl)methyl)-4-(difluoromethyl)-4-(5-(diphenylmethyleneamino)-2-fluorophenyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (intermediate E8.1) (525 mg, 723 μmol) in dichloromethane (20 ml) was added at 23° C. trifluoroacetic acid (4.12 g, 2.79 ml, 36.2 mmol) and the mixture was stirred at 23° C. for 1 hour, whereupon 1 M HCl (14.5 ml, 14.5 mmol) and dioxane (40 ml) were added and the mixture was stirred vigorously at 23° C. for 60 hours. Poured into 1 M Na2CO3-solution, extracted with dichloromethane, washed the organic layer with brine and dried over Na2SO4. Removal of the solvent in vacuum left a brown oil. The residue was purified by chromatography on 5 g silica gel with dichloromethane/methanol/ammonium hydroxide 110:10:1 to give (S)-4-(5-amino-2-fluorophenyl)-4-(difluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (82 mg, 316 μmol, 43.7% yield) as a light brown solid. MS (ISP): m/z=259.9 [M+H]+.

Workup

  1. additionwere added
  2. extractionextracted with dichloromethane
  3. washwashed the organic layer with brine
  4. dry with materialdried over Na2SO4
  5. customRemoval of the solvent in vacuum
  6. waitleft a brown oil
  7. customThe residue was purified by chromatography on 5 g silica gel with dichloromethane/methanol/ammonium hydroxide 110:10:1

Sources & evidence

ORD record
ord-c4a01f4ae52846f5a30e3cef5349ca4d
Source dataset
uspto-grants-2015_03
Patent number
US08987255B2

Reaction notes

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