1,2-Dichloroethane → tert-butyl (2R)-1-(4-(4-chloro-3-methoxyphenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

HRID 1820208Notes

Reaction equation

HRID 1820208 reaction equation
[C:1]([NH:8][C@@H:9]([C:13]([OH:15])=O)[CH:10]([CH3:12])[CH3:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2([OH:46])[CH2:43][CH2:42][NH:41][CH2:40][C:39]2([CH3:45])[CH3:44])=[CH:34][C:33]=1[O:47][CH3:48].CCN(C(C)C)C(C)C>ClCCl>[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2([OH:46])[CH2:43][CH2:42][N:41]([C:13](=[O:15])[C@H:9]([NH:8][C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7])[CH:10]([CH3:11])[CH3:12])[CH2:40][C:39]2([CH3:44])[CH3:45])=[CH:34][C:33]=1[O:47][CH3:48]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 637605(2R)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoic acidHCID 672997744-(4-Chloro-3-methoxyphenyl)-3,3-dimethylpiperidin-4-ol hydrochloride

Product 1

HCID 57889049tert-butyl (2R)-1-(4-(4-chloro-3-methoxyphenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamateYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-Boc-D-valine (85 mg, 0.39 mmol), EDC (75 mg, 0.39 mmol), HOBt (53 mg, 0.39 mmol) was dissolved in dichloromethane (2 mL). 4-(4-Chloro-3-methoxyphenyl)-3,3-dimethylpiperidin-4-ol hydrochloride (100 mg, 0.33 mmol) was added followed by DIPEA (136 μL, 0.78 mmol) and the solution was stirred at rt for 10 min. The reaction was concentrated and the resulting oily residue was purified via column chromatography (10% to 50% EtOAc/heptane) to furnish tert-butyl (2R)-1-(4-(4-chloro-3-methoxyphenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (153 mg, 99% yield) MS found: (M-Boc)+=396.3.

Workup

  1. concentrationThe reaction was concentrated
  2. customthe resulting oily residue was purified via column chromatography (10% to 50% EtOAc/heptane)

Sources & evidence

ORD record
ord-1f52e3aa4c6f45d7ac75a3468f8be7db
Source dataset
uspto-grants-2009_10
Patent number
US07601844B2

Reaction notes

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