Methanol → tert-butyl (2R,5R)-5-(azidomethyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

HRID 629720

Reaction equation

HRID 629720 reaction equation
[NH2:1][CH2:2][C@H:3]1[N:8]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:7][C@@H:6]([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[NH:24][C:25](=[O:45])[C@H:26]([CH:32]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[NH:27][C:28]([O:30][CH3:31])=[O:29])[O:5][CH2:4]1.C(=O)(O)[O-].[Na+].S([N:58]=[N+:59]=[N-])(C(F)(F)F)(=O)=O.CO>C(Cl)Cl.O.S([O-])([O-])(=O)=O.[Cu+2]>[N:1]([CH2:2][C@H:3]1[N:8]([C:9]([O:11][C:12]([CH3:14])([CH3:15])[CH3:13])=[O:10])[CH2:7][C@@H:6]([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[NH:24][C:25](=[O:45])[C@H:26]([CH:32]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[NH:27][C:28]([O:30][CH3:31])=[O:29])[O:5][CH2:4]1)=[N+:58]=[N-:59]

Participants

8

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 10986786Methanesulfonyl azide, trifluoro-HCID 86726318tert-butyl (2R,5R)-5-(aminomethyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

Product 1

HCID 86726323tert-butyl (2R,5R)-5-(azidomethyl)-2-[2-(2-{[N-(methoxycarbonyl)-beta-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate

Reagents, catalysts & solvents 3

HCID 24462Copper SulfateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl (2R,5R)-5-(aminomethyl)-2-[2-(2-{[N-(methoxycarbonyl)-β-phenyl-L-phenylalanyl]amino}phenyl)ethyl]morpholine-4-carboxylate (1 eq.) in CH2Cl2 (0.4M) was added copper(II) sulfate (0.02 eq.) and sodium bicarbonate (1 eq.) as a solution in water (NaHCO3/CuSO4)) (1M). To that mixture was added triflic azide (3.65 eq.) as a solution in CH2Cl2 (0.4M). The heterogenous mixture was homogenized by the addition of methanol and the reaction was stirred at room temperature for 30 minutes. Upon completion by LCMS, solvents were evaporated and the evaporation residue was used as such for next step.

Workup

  1. customUpon completion by LCMS, solvents were evaporated

Sources & evidence

ORD record
ord-c2ea0a96f46c46179bbcc94fdf00c96a
Source dataset
uspto-grants-2016_04
Patent number
US09315475B2

Linked notes

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