Ethyl Acetate → 2-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropan-1-ol

HRID 1530380ノート

反応式

HRID 1530380 の反応式
C[O:2][C:3](=O)[C:4]([N:7]1[CH2:12][CH2:11][CH:10]([S:13][C:14]2[C:15]([F:37])=[CH:16][C:17]3[O:26][CH2:25][CH2:24][N:23]4[C:19](=[N:20][C:21]([C:27]5[N:28]([CH:33]([CH3:35])[CH3:34])[N:29]=[C:30]([CH3:32])[N:31]=5)=[CH:22]4)[C:18]=3[CH:36]=2)[CH2:9][CH2:8]1)([CH3:6])[CH3:5].[H-].[H-].[H-].[H-].[Li+].[Al+3].CCOC(C)=O>C1COCC1>[F:37][C:15]1[C:14]([S:13][CH:10]2[CH2:11][CH2:12][N:7]([C:4]([CH3:6])([CH3:5])[CH2:3][OH:2])[CH2:8][CH2:9]2)=[CH:36][C:18]2[C:19]3[N:23]([CH2:24][CH2:25][O:26][C:17]=2[CH:16]=1)[CH:22]=[C:21]([C:27]1[N:28]([CH:33]([CH3:35])[CH3:34])[N:29]=[C:30]([CH3:32])[N:31]=1)[N:20]=3

参加物

5

反応物 3

HCID 8857Ethyl AcetateHCID 21226445Aluminium lithium hydrideHCID 683130922-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropionic acid methyl ester

生成物 1

HCID 683131162-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropan-1-ol収率 73%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To an ice-cooled solution of 2-{4-[8-fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropionic acid methyl ester (0.394 mmol) in THF (20 mL) was added LiAlH4 (1.0M in THF, 0.79 mL) and the mixture was stirred at 0° C. for 5 min. To the reaction mixture was added EtOAc (1 mL) and stirring was continued for 10 min. Volatiles were removed under reduced pressure and the resulting residue was partitioned between DCM (40 mL) and 10% aq. solution of Rochelle's salt (50 mL). The suspension was then filtered through a pad of Celite®. The filtrate was extracted with additional DCM and the combined organic layers were washed with water, then brine, dried and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-10% 2M NH3/MeOH in DCM) affording 2-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropan-1-ol (148 mg, 73% over two steps). LCMS: RT 2.17 min [M+H]+ 515.0

後処理

  1. stirringstirring
  2. waitwas continued for 10 min
  3. customVolatiles were removed under reduced pressure
  4. customthe resulting residue was partitioned between DCM (40 mL) and 10% aq. solution of Rochelle's salt (50 mL)
  5. filtrationThe suspension was then filtered through a pad of Celite®
  6. extractionThe filtrate was extracted with additional DCM
  7. washthe combined organic layers were washed with water
  8. dry with materialbrine, dried
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 2-10% 2M NH3/MeOH in DCM)

出典と根拠

ORDレコード
ord-928e2dcb8d5f4341aad48b4b839ba7e7
出典データセット
uspto-grants-2015_07
特許番号
US09090628B2

反応ノート

読み込み中…