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

HRID 1516325노트

반응식

HRID 1516325 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-3809c7f988284d59bd6339e466ef7ebe
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08227468B2

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