1,2-Dichloroethane → di-tert-butyl [(3R)-6-(2,3-dichlorophenyl)-2-oxoazepan-3-yl]imidodicarbonate

HRID 20122Notes

Reaction equation

HRID 20122 reaction equation
[C:1]([O:5][C:6]([N:8]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@@H:9]([C:23](OCC1C=CC=CC=1)=[O:24])[CH2:10][CH2:11][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:16]=1[Cl:22])[CH2:13][NH2:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CO.O.C(Cl)Cl>[Cl:22][C:16]1[C:17]([Cl:21])=[CH:18][CH:19]=[CH:20][C:15]=1[CH:12]1[CH2:13][NH:14][C:23](=[O:24])[C@H:9]([N:8]([C:33]([O:35][C:36]([CH3:39])([CH3:37])[CH3:38])=[O:34])[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:10][CH2:11]1

Participants

11

Reactant 7

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 86595032Benzyl N2,N2-bis(tert-butoxycarbonyl)-5-(2,3-dichlorophenyl)-D-lysinate

Product 1

HCID 66939423di-tert-butyl [(3R)-6-(2,3-dichlorophenyl)-2-oxoazepan-3-yl]imidodicarbonateYield 82.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution benzyl N2,N2-bis(tert-butoxycarbonyl)-5-(2,3-dichlorophenyl)-D-lysinate (0.45 g, 0.77 mmol) in MeOH (4 mL) and water (2 mL) was added 1N NaOH (3.1 mL, 3.1 mmol). This solution was heated to 40° C. for 6 h, then neutralized with 1N HCl and concentrated. To a solution of this residue in DCM (10 mL) were added EDC (0.19 g, 0.97 mmol) and HOAT (53 mg, 0.39 mmol) followed by triethylamine (0.32 mL, 0.73 mmol). After 2 h, NaHCO3 was added, the layers separated and the aqueous phase backwashed with DCM. The combined organics were dried over magnesium sulfate, filtered and concentrated. This residue was purified by silica gel chromatography (0.5%→10% MeOH/DCM) to give di-tert-butyl [(3R)-6-(2,3-dichlorophenyl)-2-oxoazepan-3-yl]imidodicarbonate (300 mg). MS 473 (M+1). Standard deprotection of a portion of this material gave the title product. MS 273 (M+1).

Workup

  1. concentrationconcentrated
  2. customthe layers separated
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThis residue was purified by silica gel chromatography (0.5%→10% MeOH/DCM)

Sources & evidence

ORD record
ord-7544af46768e4b6bacead6c0637209a9
Source dataset
uspto-grants-2010_06
Patent number
US07745427B2

Reaction notes

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