tert-Butyl methyl ether → N-[(3R,4S)-6-Bromo-3-hydroxy-chroman-4-yl]-4-fluoro-benzamide

HRID 1516325ノート

反応式

HRID 1516325 の反応式
[NH2:1][C@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Br:12])[CH:10]=2)[O:5][CH2:4][C@@H:3]1[OH:13].C(=O)(O)[O-].[Na+].[F:19][C:20]1[CH:28]=[CH:27][C:23]([C:24](Cl)=[O:25])=[CH:22][CH:21]=1.C(OC)(C)(C)C>O1CCCC1.O>[Br:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[O:5][CH2:4][C@H:3]([OH:13])[C@H:2]2[NH:1][C:24](=[O:25])[C:23]1[CH:27]=[CH:28][C:20]([F:19])=[CH:21][CH:22]=1

参加物

7

反応物 4

HCID 15413tert-Butyl methyl etherHCID 678794-Fluorobenzoyl chlorideHCID 516892Sodium BicarbonateHCID 67280416(3R,4S)-4-Amino-6-bromochroman-3-ol

生成物 1

HCID 67281102N-[(3R,4S)-6-Bromo-3-hydroxy-chroman-4-yl]-4-fluoro-benzamide収率 221.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

To a suspension of (3R,4S)-4-amino-6-bromo-chroman-3-ol (692 g, 2.84) and sodium bicarbonate (476 g, 5.67 mol) in tetrahydrofuran (3.0 L) and water (3.0 L) at 17° C. add 4-fluorobenzoyl chloride (369 mL, 3.12 mol) dropwise via addition funnel over 15 min. and stir for 2 hr. Add water (2 L) and methyl tert-butyl ether (3.5 L) and stir for 5 min. Separate the organic phase and wash it with water (2 L) and brine (2 L). Dry the organic portion over anhydrous magnesium sulfate and concentrate in vacuo to obtain a pale yellow solid (2.3 kg). Triturate the solid in heptane (5 L) at 25° C. for 3 h. Collect by filtration and dry in an oven at 50° C. for 12 hr. to obtain the title compound (975 g, 94%) as a white solid. LC-ES/MS m/z (79Br/81Br) 366/368 [M+H]+.

後処理

  1. additiondropwise via addition funnel over 15 min.
  2. customSeparate the organic phase
  3. washwash it with water (2 L) and brine (2 L)
  4. dry with materialDry the organic portion over anhydrous magnesium sulfate
  5. concentrationconcentrate in vacuo

出典と根拠

ORDレコード
ord-3809c7f988284d59bd6339e466ef7ebe
出典データセット
uspto-grants-2012_07
特許番号
US08227468B2

反応ノート

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