Hydrochloric Acid → HCID 44376209, compound

HRID 1977050Notes

Reaction equation

HRID 1977050 reaction equation
[OH:1][CH2:2][C@@H:3]1[CH2:19][N:7]2[CH2:8][CH2:9][N:10]([C:12]3[N:17]=[CH:16][C:15]([F:18])=[CH:14][N:13]=3)[CH2:11][C@@H:6]2[CH2:5][CH2:4]1.[F:20][C:21]1[CH:26]=[CH:25][C:24](O)=[CH:23][CH:22]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.Cl>C1COCC1.C(OCC)(=O)C.C(OCC)C>[F:20][C:21]1[CH:26]=[CH:25][C:24]([O:1][CH2:2][C@@H:3]2[CH2:19][N:7]3[CH2:8][CH2:9][N:10]([C:12]4[N:13]=[CH:14][C:15]([F:18])=[CH:16][N:17]=4)[CH2:11][C@@H:6]3[CH2:5][CH2:4]2)=[CH:23][CH:22]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 97324-FluorophenolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 54484575HCID 54484575, compound

Product 1

HCID 44376209HCID 44376209, compoundYield 44.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 0.82 g (3.08 mmol) of (7S,9aS)-7-hydroxymethyl-2-(5-fluoropyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine (Preparation 13), 0.52 g (4.62 mmol) of 4-fluorophenol, 0.97 g (3.70 mmol) of triphenylphosphine in dry THF was treated with 0.64 g (3.70 mmol) of diethyl azodicarboxylate and stirred at room temperature for 72 h. The solvent was evaportated, the residue dissolved in 50:50 ethyl acetate:ethyl ether, and treated with HCl(g) in ethyl ether until precipitation ceased. The solid was collected by filtration, dissolved in chloroform, 1M sodium hydroxide was added, and the layers were separated. The organic layer was dried (magnesium sulfate), filtered and evaporated. Purification by flash silica gel chromatography with 90:10 hexane:ethyl acetate gave 0.49 g (44%) of the title compound. mp (—HCl) 225-228° C. 13C NMR (base, CDCl3): δ24.8, 25.2, 33.8, 44.3, 49.7, 54.8, 56.6, 61.0, 69.5, 115.48, 115.53, 115.59, 115.83, 144.97, 145.26, 149.85, 153.15, 155.42, 155.54, 158.69, 158.74. HRMS calcd for C19H22F2N4O: 360.1762, found: 360.1752.

Workup

  1. filtrationThe solid was collected by filtration
  2. dissolutiondissolved in chloroform
  3. addition1M sodium hydroxide was added
  4. customthe layers were separated
  5. dry with materialThe organic layer was dried (magnesium sulfate)
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by flash silica gel chromatography with 90:10 hexane

Sources & evidence

ORD record
ord-04a39ae6aa094df88e99050d61a9fcfc
Source dataset
uspto-grants-2001_05
Patent number
US06231833B1

Reaction notes

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