Diisopropylethylamine → (S)-1-((R)-2,3-Dihydrobenzo[1,4]dioxine-2-carbonyl)-3-methylpiperidine-3-carboxylic acid ethyl ester

HRID 2407304Notes

Reaction equation

HRID 2407304 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][C@@H:2]1[C:11](Cl)=[O:12].[CH2:14]([O:16][C:17]([C@@:19]1([CH3:25])[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]1)=[O:18])[CH3:15].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:14]([O:16][C:17]([C@@:19]1([CH3:25])[CH2:24][CH2:23][CH2:22][N:21]([C:11]([C@@H:2]2[O:1][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[O:4][CH2:3]2)=[O:12])[CH2:20]1)=[O:18])[CH3:15]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7022160(R)-2,3-Dihydrobenzo[1,4]dioxine-2-carbonyl chlorideHCID 23389262(S)-Ethyl 3-methylpiperidine-3-carboxylate

Product 1

HCID 66727067(S)-1-((R)-2,3-Dihydrobenzo[1,4]dioxine-2-carbonyl)-3-methylpiperidine-3-carboxylic acid ethyl esterYield 99.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

(R)-2,3-Dihydrobenzo[1,4]dioxine-2-carbonyl chloride (6.05 g, 30.5 mmol) in DCM (20 ml) was added to a stirred mixture of (S)-3-methyl-piperidine-3-carboxylic acid ethyl ester (5.0 g, 29.2 mmol), DIPEA (5.5 ml, 31.7 mmol) and DCM (30 ml), previously cooled down to 5° C. The cooling bath was removed and stirring continued at RT for 1 h. The reaction mixture was washed twice with 1 M HCl, twice with sat. aq NaHCO3 and twice with water and dried with Na2SO4. Solvent was evaporated to give 9.66 g of the title compound.

Workup

  1. customThe cooling bath was removed
  2. washThe reaction mixture was washed twice with 1 M HCl, twice with sat. aq NaHCO3 and twice with water
  3. dry with materialdried with Na2SO4
  4. customSolvent was evaporated

Sources & evidence

ORD record
ord-09a729b1297248b2aa7ffe9e492cd97b
Source dataset
uspto-grants-2014_08
Patent number
US08809536B2

Reaction notes

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