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 1525871ノート

反応式

HRID 1525871 の反応式
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

参加物

6

反応物 4

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

生成物 1

HCID 712708922-(4-Bromo-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetic acid収率 47.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-c27df34ea15e4dfb801cd6b24d98d8d3
出典データセット
uspto-grants-2015_07
特許番号
US09084794B2

反応ノート

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