1,8-Diazabicyclo(5.4.0)undec-7-ene → Racemic (7S*,9aS*)-2-(Benzo[d]isoxazol-3-yl)perhydro-7-(hydroxymethyl)-1H-pyrido[1,2-a]pyrazine

HRID 466587Notes

Reaction equation

HRID 466587 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:12][N:7]2[CH2:8][CH2:9][NH:10][CH2:11][CH:6]2[CH2:5][CH2:4]1.Cl[C:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[O:16][N:15]=1.N12CCCN=C1CCCCC2>N1C(C)=CC=CC=1C>[O:16]1[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:14]([N:10]2[CH2:9][CH2:8][N:7]3[CH2:12][CH:3]([CH2:2][OH:1])[CH2:4][CH2:5][CH:6]3[CH2:11]2)=[N:15]1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27797803-Chloro-1,2-benzoxazoleHCID 12985539(Octahydro-1H-pyrido[1,2-A]pyrazin-7-YL)methanol

Product 1

HCID 22491366Racemic (7S*,9aS*)-2-(Benzo[d]isoxazol-3-yl)perhydro-7-(hydroxymethyl)-1H-pyrido[1,2-a]pyrazineYield 41.7%

Reagents, catalysts & solvents 1

HCID 79372,6-LutidineSolvent

Conditions

Temperature
145 °C

Procedure

A mixture consisting of racemic (7S*,9aS*)-7-(hydroxymethyl)perhydro-1H-pyrido[1,2-a]pyrazine (see Example 27; 500 mg, 2.93 mmol), 3-chloro-1,2-benzisoxazole (890 mg, 5.86 mmol) and 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU, 446 mg, 0.438 ml, 2.93 mmol) in 2,6-lutidine (0.5 ml) was stirred and heated at 145° C. for 18 hours. The solvent was removed in vacuo, and the tarry residue was thoroughly extracted with methylene chloride (150 ml). Insolubles were filtered and the solvent was removed in vacuo to afford a dark brown residue. Flash chromatography of the entire sample (20 g silica gel, 32-63 mesh; eluting with ethyl acetate/methanol=95:5 in volume) afforded 350 mg (41.7%) of the title compound (in which the 7- and 9a-hydrogen substituents remain cis) as a colorless amorphous solid. HRMS m/z 287.1639 (M, C16H21N3O2). 13CNMR (CDCl3) delta 164.0, 161.0, 129.5, 122.3, 122.1, 116.1, 110.5, 67.5, 60.2, 58.2, 54.2, 53.7, 48.3, 34.4, 26.9, 26.3.

Workup

  1. customThe solvent was removed in vacuo
  2. extractionthe tarry residue was thoroughly extracted with methylene chloride (150 ml)
  3. filtrationInsolubles were filtered
  4. customthe solvent was removed in vacuo
  5. customto afford a dark brown residue
  6. washFlash chromatography of the entire sample (20 g silica gel, 32-63 mesh; eluting with ethyl acetate/methanol=95:5 in volume)

Sources & evidence

ORD record
ord-faa9fa4a0feb48e097e5ef68b204f967
Source dataset
uspto-grants-1992_10
Patent number
US05157034

Reaction notes

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