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

HRID 967547Notes

Reaction equation

HRID 967547 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). Essentially following the procedures outlined for the preparation of Intermediate 57, the Intermediates in Table I-3 were prepared. Compounds along the route to the Intermediates in Table I-3, can be further processed (e.g. alkylation of N1) according to those skilled in the art following essentially the same procedures as outlined above to afford another set of intermediates.

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-dbd93ce5242c4e57b24804ec0467a16a
Source dataset
uspto-grants-2005_10
Patent number
US06953790B2

Reaction notes

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