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 1016138Notes

Reaction equation

HRID 1016138 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-25ac27056a7e4f5b8cddd7366ca1fc09
Source dataset
uspto-grants-2011_07
Patent number
US07985861B2

Reaction notes

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