4-Methylmorpholine → HCID 86619280, compound

HRID 2267674Notes

Reaction equation

HRID 2267674 reaction equation
[C:1]1([C@@H:7]2[O:9][C@H:8]2[C:10]([O-:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[K+].[CH:14]1[CH:15]=CC2N(O)N=N[C:18]=2[CH:19]=1.C[N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.[CH3:31][CH2:32]N=C=NCCCN(C)C.Cl>C1COCC1>[CH:29]1([CH2:30][N:25]([C@@H:26]2[CH2:18][CH2:19][CH2:14][CH2:15][C@H:27]2[OH:28])[C:10]([C@H:8]2[C@H:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:9]2)=[O:12])[CH2:32][CH2:31]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23702683HCID 23702683, compound

Product 1

HCID 86619280HCID 86619280, compoundYield 66.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (1,2-trans)-2-[(cyclopropylmethyl)amino]cyclohexanol (117a) (4.34 g, 25.6 mmol) in THF (100 mL) was added potassium (2R,3S)-3-phenyloxirane-2-carboxylate (64a) (5.06 g, 25.0 mmol), HOBt (4.20 g, 27.4 mmol), NMM (8.25 mL, 75.0 mmol) and EDAC-HCl (5.94 g, 31.0 mmol). The mixture was stirred at ambient temperature under nitrogen overnight. The solvent was evaporated and the residue was purified by flash chromatography on silica gel eluting with dichloromethane ethyl acetate (3:1 then 1:1) followed by 10% methanol/dichloromethane to afford the title compound as a sticky white gum (5.22 g, 66%). The foam when dissolved in a little ether gave, on standing at RT overnight, a white solid (1.65 g, 21%), mp 110-120° C. TLC Rf˜0.50 (4:1 hexane:ether). 1H NMR (300 MHz, CDCl3) δ0.19-0.41 (m, 2H), 0.53-0.59 (m, 2H), 0.80-1.37 (m, 4H), 1.45-1.60 (m, 1H), 1.65-1.86 (m, 3H), 2.03-2.18 (m, 2H), 3.10-3.82 (m, 4H), 3.99-4.13 (m, 1H), 7.36 (m, 5H). HPLC (Method B): 3.67 min. On standing in the HPLC vial the 3.67 min peak diminished and a peak at 4.57 min (117c) increased.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by flash chromatography on silica gel eluting with dichloromethane ethyl acetate (3:1

Sources & evidence

ORD record
ord-ff51d798ed9747fb96164f16ebb83456
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

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