Potassium Carbonate → 2-(4-Bromo-2-fluorophenyl)-2-(4-(1-(hydroxymethyl)cyclopropyl)-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide

HRID 1525894Notes

Reaction equation

HRID 1525894 reaction equation
Br[CH:2]([C:6]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][C:7]=1[F:13])[C:3]([NH2:5])=[O:4].C(=O)([O-])[O-].[K+].[K+].Cl.[OH:21][CH2:22][C:23]1([N:26]2[CH2:31][C:30]3([CH2:36][CH2:35][NH:34][CH2:33][CH2:32]3)[O:29][CH2:28][C:27]2=[O:37])[CH2:25][CH2:24]1>CN(C)C=O.O>[Br:12][C:9]1[CH:10]=[CH:11][C:6]([CH:2]([N:34]2[CH2:35][CH2:36][C:30]3([O:29][CH2:28][C:27](=[O:37])[N:26]([C:23]4([CH2:22][OH:21])[CH2:24][CH2:25]4)[CH2:31]3)[CH2:32][CH2:33]2)[C:3]([NH2:5])=[O:4])=[C:7]([F:13])[CH:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 712709464-(1-(Hydroxymethyl)cyclopropyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochlorideHCID 867254262-Bromo-2-(4-bromo-2-fluorophenyl)acetamide

Product 1

HCID 712707062-(4-Bromo-2-fluorophenyl)-2-(4-(1-(hydroxymethyl)cyclopropyl)-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-bromo-2-(4-bromo-2-fluorophenyl)acetamide (1.037 mmol) in N,N-dimethylformamide (5 mL) was treated with potassium carbonate (2.96 mmol) and the crude 4-(1-(hydroxymethyl)cyclopropyl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride from Example 29a. The reaction was stirred at room temperature overnight. The reaction solution was then diluted with water (100 mL) and was extracted three times with ethyl acetate. The combined organic layers were washed three times with water, three times with brine, and was then dried over sodium sulfate, filtered and concentrated to dryness in vacuo to afford the crude title compound as a yellow oil (500 mg of 85% pure material as determined by 1H NMR, 91% yield over the two steps). MS(ES)+ m/e 470.1/472.0 [M+H]+ (bromide isotope pattern).

Workup

  1. extractionwas extracted three times with ethyl acetate
  2. washThe combined organic layers were washed three times with water, three times with brine
  3. dry with materialwas then dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness in vacuo

Sources & evidence

ORD record
ord-bee5928137a84be3ad51b60bb6649d24
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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