Diisopropylethylamine → 1-{2-[(3S,4S)-4-(2,2-Dimethyl-propionyloxy)-3-methyl-piperidin-1-yl]-ethyl}-2-oxa-3-aza-bicyclo[2.2.2]octane-3-carboxylic acid tert-butyl ester

HRID 1804767Notes

Reaction equation

HRID 1804767 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:13]2[CH2:14][CH2:15][C@:10]([CH2:16][CH2:17]O)([CH:11]=[CH:12]2)[O:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(C(C(O)=O)(O)C(C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.[CH3:45][C@@H:46]1[C@@H:51]([O:52][C:53](=[O:58])[C:54]([CH3:57])([CH3:56])[CH3:55])[CH2:50][CH2:49][NH:48][CH2:47]1.[I-].C(C[P+](C)(C)C)#N.C(N(C(C)C)CC)(C)C>C(#N)CC>[C:1]([O:5][C:6]([N:8]1[CH:13]2[CH2:14][CH2:15][C:10]([CH2:16][CH2:17][N:48]3[CH2:49][CH2:50][C@H:51]([O:52][C:53](=[O:58])[C:54]([CH3:57])([CH3:56])[CH3:55])[C@@H:46]([CH3:45])[CH2:47]3)([CH2:11][CH2:12]2)[O:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 10514344(Cyanomethyl)trimethylphosphanium iodideHCID 67361876(1S,4S)-1-(2-Hydroxy-ethyl)-2-oxa-3-aza-bicyclo[2.2.2]oct-5-ene-3-carboxylic acid tert-butyl esterHCID 1317301552,2-Dimethyl-propionic acid (3S,4S)-3-methyl-piperidin-4-yl ester (-)-dibenzoyltartrate

Product 1

HCID 591526581-{2-[(3S,4S)-4-(2,2-Dimethyl-propionyloxy)-3-methyl-piperidin-1-yl]-ethyl}-2-oxa-3-aza-bicyclo[2.2.2]octane-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 7854PropionitrileSolvent

Conditions

Temperature
120 °C

Procedure

(1S,4S)-1-(2-Hydroxy-ethyl)-2-oxa-3-aza-bicyclo[2.2.2]oct-5-ene-3-carboxylic acid tert-butyl ester (11) (620 mg, 2.41 mmol) is dissolved in 24 ml of propionitrile and after addition of amine 6 (480 mg, 2.41 mmol), cyanomethyl-trimethyl-phosphonium iodide (796 mg, 6 mmol) and diisopropyl ethyl amine (2 ml, 12 mmol) the mixture is stirred for 16 h at 120° C. Then the mixture is evaporated under reduced pressure. The residue is diluted with ethyl acetate, washed 10% K2CO3- and NaCl-solution, and dried over Na2SO4. The crude product is purified by Flash-chromatography (ethyl acetate/hexanes (9.5:0.5), silicagel).

Workup

  1. customThen the mixture is evaporated under reduced pressure
  2. additionThe residue is diluted with ethyl acetate
  3. washwashed 10% K2CO3- and NaCl-solution
  4. dry with materialdried over Na2SO4
  5. customThe crude product is purified by Flash-chromatography (ethyl acetate/hexanes (9.5:0.5), silicagel)

Sources & evidence

ORD record
ord-0f6f8bd3c01043e5946dbc0eecc6a6f5
Source dataset
uspto-grants-2013_01
Patent number
US08354431B2

Reaction notes

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