4-Methylmorpholine → HCID 86652253, compound

HRID 1887399Notes

Reaction equation

HRID 1887399 reaction equation
CN1CCOCC1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.ON1C2C=CC=CC=2N=N1.[C:42]([O:46][C:47]([NH:49][C@@H:50]([C:54]([CH3:57])([CH3:56])[CH3:55])[C:51]([OH:53])=O)=[O:48])([CH3:45])([CH3:44])[CH3:43].[CH3:58][C@@H:59]1[CH2:63][NH:62][C@@H:61]2[C@@H:64]([OH:67])[CH2:65][O:66][C@H:60]12>CN(C)C=O>[OH:67][C@@H:64]1[C@H:61]2[N:62]([C:51](=[O:53])[C@@H:50]([NH:49][C:47](=[O:48])[O:46][C:42]([CH3:43])([CH3:44])[CH3:45])[C:54]([CH3:57])([CH3:56])[CH3:55])[CH2:63][C@@H:59]([CH3:58])[C@H:60]2[O:66][CH2:65]1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2734668(S)-2-((tert-Butoxycarbonyl)amino)-3,3-dimethylbutanoic acidHCID 55286287HCID 55286287, compound

Product 1

HCID 86652253HCID 86652253, compoundYield 133.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Methylmorpholine (1.062 mL, 9.7 mmol) was added to a suspension of 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU, 1839 mg, 4.85 mmol), 1-hydroxybenzotriazole (654 mg, 4.85 mmol) and (S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoic acid (1.125 g, 4.85 mmol) in dimethylformamide (5 mL). The mixture was stirred for 5 minutes before adding to (3R,3aR,6R,6aR)-6-methylhexahydro-2H-furo[3,2-b]pyrrol-3-ol (107) (prepared as above with appropriate scaling of quantities, assume 4.62 mmol). The mixture was stirred for 16 hours then the solvents removed in vacuo. The crude product was dissolved in DCM (75 mL) then washed with (75 ML each) sat. NaHCO3, 0.01N HCl, brine and the organic layer dried over Na2SO4. The mixture was filtered to leave a tan oil (2.20 g). Flash chromatography over silica, eluting with ethyl acetate:pentane mixtures 15:85 to 50:50 gave desired alcohol as a white solid (1.45 g, contaminated with tetramethylurea). Analytical HPLC main peak, Rt=11.94 min., HPLC-MS 301.2 [M+2H−tBu]+, 357.2 [M+H]+, 379.2 [M+Na]+, 735.5 [2M+Na]+.

Workup

  1. stirringThe mixture was stirred for 16 hours
  2. customthe solvents removed in vacuo
  3. dissolutionThe crude product was dissolved in DCM (75 mL)
  4. washthen washed with (75 ML each) sat. NaHCO3, 0.01N HCl, brine
  5. dry with materialthe organic layer dried over Na2SO4
  6. filtrationThe mixture was filtered

Sources & evidence

ORD record
ord-91085eedaf854f119eeb3e22ef9ced7a
Source dataset
uspto-grants-2013_08
Patent number
US08501744B2

Reaction notes

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