Ethanol → 1268364-46-0

HRID 2400518Notes

Reaction equation

HRID 2400518 reaction equation
[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].C(O)C.[CH2:10]([O:17][CH2:18][C@@H:19]1[CH2:28][N:27]2[C@H:22]([CH2:23][O:24][CH2:25][CH2:26]2)[CH2:21][NH:20]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C(OCC)(=O)C>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[CH2:10]([O:17][CH2:18][C@@H:19]1[CH2:28][N:27]2[C@H:22]([CH2:23][O:24][CH2:25][CH2:26]2)[CH2:21][NH:20]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 971Oxalic AcidHCID 67031894HCID 67031894, compound

Product 1

HCID 679698481268364-46-0

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

A 20 L jacketed lined reactor was charged with oxalic acid (0.304 kg, 1.0 eq, based on wt/wt HPLC assay of (7S,9aS)-7-[(benzyloxy)methyl]octahydropyrazino[2,1-c][1,4]oxazine solution from Stage 5c), ethanol (200 proof, 2.75 L) and ethyl acetate (6.4 L). The mixture was heated to 60° C. and the crude ethyl acetate solution of (7S,9aS)-7-[(benzyloxy)methyl]octahydropyrazino[2,1-c][1,4]oxazine from Stage 5C was added to the reactor at a rate to maintain the temperature above 50° C. This solution was stirred at 60° C. for 30 min, cooled to 20° C. and then stirred overnight at 20° C. The solids were removed, filtered and then washed with an ethyl acetate:ethanol (6:1, 1.8 L) solution. The solids were then placed in an oven, under vacuum, at 50° C., until dry, giving the title compound as a beige crystalline solid (0.306 kg). A second crop of the title compound was obtained from the mother liquor (0.133 kg). 1H NMR (DMSO-d6) δ 9.5-8.5 (br s, 4H) 7.41-7.36 (m, 3H), 7.35-7.27 (m, 2H), 4.57 (d, J=2.0 Hz, 2H), 3.94 (t, J=8.3 Hz, 1H), 3.76-3.61 (m, 4H), 3.45 (ddd, J=13.9, 11.7, 2.2 Hz, 1H), 3.06 (t, J=11.8 Hz, 1H), 2.94 (dd, J=12.7, 2.9 Hz, 1H), 2.79 (d, J=12.4 Hz, 1H), 2.67 (t, J=12.5 Hz, 1H), 2.56 (d, J=11.4, 1H), 2.43 (dd, J=12.7, 3.4 Hz, 1H), 2.39-2.29 (m, 1H), 2.14 (ddd, J=14.9, 11.5, 3.2 Hz, 1H).

Workup

  1. temperatureto maintain the temperature above 50° C
  2. temperaturecooled to 20° C.
  3. stirringstirred overnight at 20° C
  4. customThe solids were removed
  5. filtrationfiltered
  6. washwashed with an ethyl acetate:ethanol (6:1, 1.8 L) solution
  7. customThe solids were then placed in an oven, under vacuum, at 50° C.
  8. customuntil dry

Sources & evidence

ORD record
ord-6e19a297880140a69ae453f2b1ef4560
Source dataset
uspto-grants-2014_08
Patent number
US08796269B2

Reaction notes

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