Sodium Hydroxide → 2-(4-Bromophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetic acid

HRID 1525849Notes

Reaction equation

HRID 1525849 reaction equation
Cl.[CH:2]1([N:5]2[CH2:10][C:9]3([CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[O:8][CH2:7][C:6]2=[O:16])[CH2:4][CH2:3]1.[OH-].[Na+].O.O=[CH:21][C:22]([OH:24])=[O:23].[Br:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1>ClCCl>[Br:25][C:26]1[CH:31]=[CH:30][C:29]([CH:21]([N:13]2[CH2:12][CH2:11][C:9]3([O:8][CH2:7][C:6](=[O:16])[N:5]([CH:2]4[CH2:4][CH2:3]4)[CH2:10]3)[CH2:15][CH2:14]2)[C:22]([OH:24])=[O:23])=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 79599(4-Bromophenyl)boronic acidHCID 15620607Glyoxylic acid, monohydrate2×HCID 69083351HCID 69083351, compound

Product 1

HCID 712707412-(4-Bromophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetic acidYield 18%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 4-cyclopropyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride (8.11 mmol) in dichloromethane (20 mL) was treated with 1N aq sodium hydroxide (10 mL) at room temperature. After stirring for one hour, the dichloromethane layer had turned clear. The mixture was transferred to a separatory funnel and the organic phase was removed. The aqueous layer was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The resulting yellow oil was dissolved in dichloromethane (20 mL) and treated with 2-oxoacetic acid monohydrate (8.11 mmol) and (4-bromophenyl)boronic acid (8.11 mmol) at room temperature. The reaction was allowed to stir at room temperature for 4 days, at which point an additional equivalent of 2-oxoacetic acid monohydrate (8.11 mmol) was added. The reaction was allowed to stir overnight, at which point the suspension was concentrated in vacuo. Purification of the residue by reverse phase HPLC (5-30% acetonitrile/water with 0.1% NH4OH) afforded the title compound as a white solid (18%). MS(ES)+ m/e 422.9/424.8 [M+H]+ (bromide isotope pattern).

Workup

  1. customThe mixture was transferred to a separatory funnel
  2. customthe organic phase was removed
  3. extractionThe aqueous layer was extracted twice with dichloromethane
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting yellow oil was dissolved in dichloromethane (20 mL)
  8. additionwas added
  9. stirringto stir overnight, at which point the suspension
  10. concentrationwas concentrated in vacuo
  11. customPurification of the residue by reverse phase HPLC (5-30% acetonitrile/water with 0.1% NH4OH)

Sources & evidence

ORD record
ord-138cb9b57d234b748b300f9773b1d6e4
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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