Hydrochloric Acid → 2-[4-(1-Methyl-3-piperidin-1-ylpropoxy)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-ene

HRID 251464Notes

Reaction equation

HRID 251464 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[N:34]1([CH2:40][CH2:41][CH:42]([OH:44])[CH3:43])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1.[N:45]1[C:49]2([CH2:54][CH2:53][CH2:52][CH2:51][CH2:50]2)[CH2:48][O:47][C:46]=1[C:55]1[CH:60]=[CH:59][C:58](O)=[CH:57][CH:56]=1.Cl>O1CCCC1>[CH3:43][CH:42]([O:44][C:58]1[CH:59]=[CH:60][C:55]([C:46]2[O:47][CH2:48][C:49]3([CH2:54][CH2:53][CH2:52][CH2:51][CH2:50]3)[N:45]=2)=[CH:56][CH:57]=1)[CH2:41][CH2:40][N:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 13155989alpha-Methyl-1-piperidinepropanolHCID 1355265344-(3-Oxa-1-azaspiro[4.5]dec-1-en-2-yl)phenol

Product 1

HCID 119500192-[4-(1-Methyl-3-piperidin-1-ylpropoxy)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-eneYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of triphenylphosphine (1.03 g, 3.92 mmol, 1.1 eq) in tetrahydrofuran (10 ml) at 0° C. is added dropwise diisopropylazodicarboxylate (0.776 ml, 3.92 mmol, 1.1 eq). The mixture is stirred for 5 minutes and 4-(1-piperidinyl)-2-butanol (0.56 g, 3.56 mmol, 1 eq) is added slowly. Then, a solution of 4-(3-oxa-1-azaspiro[4.5]dec-1-en-2-yl)phenol ax8 (0.82 g, 3.56 mmol, 1 eq) in tetrahydrofuran (5 ml) is added at 0° C. The mixture is allowed to warm at room temperature and stirred for 2 hours. It is then poured into 0.5 N hydrochloric acid and extracted with diethyl ether. The aqueous layer is treated with a 1 M aqueous solution of sodium hydroxide to reach pH 9 and extracted 3 times with diethyl ether. The combined organic layers are dried over magnesium sulfate and the solvent is removed under reduced pressure to give 1.18 g of an orange oil. The crude product is purified by chromatography over silica gel to give 0.41 g of 2-[4-(1-methyl-3-piperidin-1-ylpropoxy)phenyl]-3-oxa-1-azaspiro[4.5]dec-1-ene 37 as a yellow oil.

Workup

  1. stirringstirred for 2 hours
  2. extractionextracted with diethyl ether
  3. additionThe aqueous layer is treated with a 1 M aqueous solution of sodium hydroxide
  4. extractionextracted 3 times with diethyl ether
  5. dry with materialThe combined organic layers are dried over magnesium sulfate
  6. customthe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-42c8b73f6c604effa5f55655e05b5739
Source dataset
uspto-grants-2011_01
Patent number
US07863450B2

Reaction notes

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