Dimethyl Sulfoxide → 4-[7-(Azetidin-3-yloxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 657270Notes

Reaction equation

HRID 657270 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([OH:6])[CH2:3]1.CC([O-])(C)C.[K+].CS(C)=O.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([C:30]2[C:39]3[C:34](=[CH:35][C:36](F)=[CH:37][CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]>O>[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([C:30]2[C:39]3[C:34](=[CH:35][C:36]([O:6][CH:4]4[CH2:5][NH:2][CH2:3]4)=[CH:37][CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 27592903-Hydroxyazetidine hydrochlorideHCID 23665647Potassium tert-butoxideHCID 595517364-(7-Fluoro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 595517494-[7-(Azetidin-3-yloxy)-quinazolin-4-yl]-piperidine-1-carboxylic acid tert-butyl esterYield 106%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of Azetidin-3-ol hydrochloride (Oakwood) (461 mg, 4.21 mmol), KOtBu (1.02 g, 9.11 mmol), and dry DMSO (4.2 mL) was stirred at rt for 30 min until a translucent solution resulted. Then 4-(7-fluoro-quinazolin-4-yl)-piperidine-1-carboxylic acid tert-butyl ester (1.46 g, 4.41 mmol), as prepared in Example 65b, was added, and the resulting opaque orange mixture (no visible precipitate) was stirred at rt for 3.5 hr. The reaction was then shaken with water (40 mL) and extracted with DCM (1×20 mL) and 9:1 DCM/MeOH (1×20 mL). The combined organic layers were washed with 0.2 M K2CO3 (3×20 mL), dried (Na2SO4), and concentrated to give 1.715 g of the title compound as an off-white solid (“106%” crude yield). LC/MS (ESI): calcd mass 384.2, found 385.3 (MH)+.

Workup

  1. customresulted
  2. additionwas added
  3. stirringthe resulting opaque orange mixture (no visible precipitate) was stirred at rt for 3.5 hr
  4. extractionextracted with DCM (1×20 mL) and 9:1 DCM/MeOH (1×20 mL)
  5. washThe combined organic layers were washed with 0.2 M K2CO3 (3×20 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-bec04a8afd524fe2961289371f08501b
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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