1,2-Dichloroethane → HCID 67386128, compound

HRID 1898529Notes

Reaction equation

HRID 1898529 reaction equation
[C:1]([NH:8][C@@H:9]([C:14]([OH:16])=O)[C:10]([CH3:13])([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[OH:17][C:18]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:4]([O:3][C:1](=[O:2])[NH:8][C@@H:9]([C:14]([N:21]1[CH2:22][CH2:23][C:18]([OH:17])([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:19][CH2:20]1)=[O:16])[C:10]([CH3:11])([CH3:12])[CH3:13])([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 963874-Phenylpiperidin-4-olHCID 7005057(2R)-2-{[(tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acid

Product 1

HCID 67386128HCID 67386128, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A round-bottomed flask was charged with Boc-D-tert-leucine (0.30 g, 1.3 mmol, 4-hydroxy-4-phenylpiperidine (345 mg, 1.95 mmol), HOBT (218 mg, 1.43 mmol) and EDC (274 mg, 1.43 mmol). Then added DMF (6 mL) followed by N,N-diisopropylethylamine (0.34 mL, 1.95 mmol). The light yellow reaction mixture was stirred at room temperature overnight then quenched with water and extracted with diethyl ether (2×). The organic layers were combined and washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over 24 g SiO2 with 0-40% EtOAc/heptane to give 0.48 g (95%) of [(R)-1-(4-hydroxy-4-phenyl-piperidine-1-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester as an off-white foam.

Workup

  1. customthen quenched with water
  2. extractionextracted with diethyl ether (2×)
  3. washwashed twice with water and once with brine
  4. dry with materialthen dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography over 24 g SiO2 with 0-40% EtOAc/heptane

Sources & evidence

ORD record
ord-3b234781b4344b7988e5176f62d5199f
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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