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

HRID 1525871Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1525871
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)=[C:28]([F:35])[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])=[C:28]([F:35])[CH:27]=1

Komponenten

6

Edukt 4

HCID 14798Sodium HydroxideHCID 27733334-Bromo-2-fluorobenzeneboronic acidHCID 15620607Glyoxylic acid, monohydrateHCID 69083351HCID 69083351, Verbindung

Produkt 1

HCID 712708922-(4-Bromo-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetic acidAusbeute 47,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A suspension of 4-cyclopropyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one hydrochloride (4.05 mmol) in dichloromethane (10 mL) was treated with 1N aq sodium hydroxide (5.00 mmol) at room temperature. After one hour the organic layer of the reaction had turned from cloudy to clear. The aqueous layer was removed via pipet. To the remaining organic solution was added 2-oxoacetic acid monohydrate (4.05 mmol) and (4-bromo-2-fluorophenyl)boronic acid (4.05 mmol) at room temperature. The reaction was allowed to stir at room temperature for three days, after which the solution was concentrated to dryness under a stream of nitrogen. The resulting crude material was diluted with acetonitrile (10 mL) and transferred to a microwave reactor vial. The reaction vessel was sealed and the mixture irradiated in a Biotage Initiator Microwave at 80° C. for 30 min and then at 100° C. for 30 min. The reaction was concentrated to dryness in vacuo. The resulting crude material was purified by reverse phase HPLC (10-40% acetonitrile/water w/0.1% NH4OH) to afford the title compound as a white solid (853 mg, 45%). MS(ES)+ m/e 441.0/443.1 [M+H]+ (bromide isotope pattern).

Aufarbeitung

  1. customThe aqueous layer was removed via pipet
  2. concentrationafter which the solution was concentrated to dryness under a stream of nitrogen
  3. additionThe resulting crude material was diluted with acetonitrile (10 mL)
  4. customtransferred to a microwave reactor
  5. customThe reaction vessel was sealed
  6. customthe mixture irradiated in a Biotage Initiator Microwave at 80° C. for 30 min
  7. waitat 100° C. for 30 min
  8. concentrationThe reaction was concentrated to dryness in vacuo
  9. customThe resulting crude material was purified by reverse phase HPLC (10-40% acetonitrile/water w/0.1% NH4OH)

Quellen und Nachweise

ORD-Eintrag
ord-c27df34ea15e4dfb801cd6b24d98d8d3
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09084794B2

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