Phenol → (7R,9aS)-7-Phenoxymethyl-2-pyrimidin-2-yl-octahydro-pyrido[1,2-a]pyrazine

HRID 1977014Notes

Reaction equation

HRID 1977014 reaction equation
[OH:1][CH2:2][C@H:3]1[CH2:18][N:7]2[CH2:8][CH2:9][N:10]([C:12]3[N:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[CH2:11][C@@H:6]2[CH2:5][CH2:4]1.[C:19]1(O)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[O:1]([CH2:2][C@H:3]1[CH2:18][N:7]2[CH2:8][CH2:9][N:10]([C:12]3[N:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[CH2:11][C@@H:6]2[CH2:5][CH2:4]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 14995231cis-(2-Pyrimidin-2-yl-octahydro-pyrido[1,2-a]pyrazin-7-yl)-methanol

Product 1

HCID 15817410(7R,9aS)-7-Phenoxymethyl-2-pyrimidin-2-yl-octahydro-pyrido[1,2-a]pyrazineYield 61.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

A solution of 0.385 g (1.55 mmol) of (7R,9aS)-7-hydroxymethyl-2-(pyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine (Preparation 4), 0.220 g (2.34 mmol) of phenol, and 0.488 g (1.86 mmol) of triphenylphosphine in 30 mL of dry THF was treated with 0.324 g (1.86 mmol) of diethyl azodicarboxylate, and the mixture stirred at 23° C. for 16 h. The solvent was evaporated, the residue dissolved in ethyl ether and treated with HCl(g) in ether. The precipitate was collected on a Büchner funnel, and washed with 1:1 ether:ethyl acetate three times. The solid was dissolved in water, basified with 1 M NaOH and extracted with chloroform. The organic layer was washed with 1 M NaOH (2×) and water (1×), dried (magnesium sulfate), filtered and evaporated to give 0.310 g of (7R,9aS)-7-phenoxymethyl-2,3,4,6,7,8,9,9a-octahydro-2-pyrimidin-2-yl-1H-pyrido[1,2-a]pyrazine. mp (HCl) 203-205° C. 13C NMR (base, CDCl3): δ27.0, 29.0, 36.4, 43.6, 49.1, 54.9, 58.8, 60.8, 70.9, 109.8, 114.5, 120.6, 129.4, 157.7, 159.0, 161.5. HRMS calcd for C19H24N4O: 324.195. Found: 324.194.

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue dissolved in ethyl ether
  3. additiontreated with HCl(g) in ether
  4. customThe precipitate was collected on a Büchner funnel
  5. washwashed with 1:1 ether
  6. dissolutionThe solid was dissolved in water
  7. extractionextracted with chloroform
  8. washThe organic layer was washed with 1 M NaOH (2×) and water (1×)
  9. dry with materialdried (magnesium sulfate)
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-23bcae86ea5147e9a8f14908264aed1b
Source dataset
uspto-grants-2001_05
Patent number
US06231833B1

Reaction notes

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