Hydrochloric Acid → 3-Azido-3-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]propanal

HRID 605767ノート

反応式

HRID 605767 の反応式
[N:1]([CH:4]([C:11]1([OH:34])[CH2:14][N:13]([C:15]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([F:24])[C:18]=2[NH:25][C:26]2[CH:31]=[CH:30][C:29]([I:32])=[CH:28][C:27]=2[F:33])=[O:16])[CH2:12]1)[CH2:5][CH:6]1OCC[O:7]1)=[N+:2]=[N-:3].Cl.C(=O)(O)[O-].[Na+]>O1CCCC1>[N:1]([CH:4]([C:11]1([OH:34])[CH2:12][N:13]([C:15]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[C:19]([F:24])[C:18]=2[NH:25][C:26]2[CH:31]=[CH:30][C:29]([I:32])=[CH:28][C:27]=2[F:33])=[O:16])[CH2:14]1)[CH2:5][CH:6]=[O:7])=[N+:2]=[N-:3]

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 866212743-[1-Azido-2-(1,3-dioxolan-2-yl)ethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol

生成物 1

HCID 866212753-Azido-3-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]propanal収率 93.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

3-[1-Azido-2-(1,3-dioxolan-2-yl)ethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol (24 mg, 0.041 mmol) was dissolved in tetrahydrofuran (0.5 mL) and treated with 5% aqueous hydrochloric acid (0.5 mL) at ambient for 15 h. The misture was neutralised with saturated sodium bicarbonate solution and was extracted twice with ethyl acetate. The combined organic portion was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford 3-azido-3-[1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-hydroxyazetidin-3-yl]propanal (21 mg, 0.0385 mmol) which was suspended in ethanol (2 mL) and treated with sodium borohydride (5 mg, 0.132 mmol) at ambient for 2 h. The mixture was quenched with acetic acid (4 drops) and concentrated in vacuo. The residue was partitioned between saturated sodium bicarbonate solution and ethyl acetate. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Column chromatography (silica gel, 70-80% ethyl acetate in hexanes) gave 3-(1-azido-3-hydroxypropyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol (14 mg, 0.0255 mmol, 62% yield from 3-[1-azido-2-(1,3-dioxolan-2-yl)ethyl]-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol): 1H NMR (400 MHz, CDCl3): 8.33 (br s, 1H), 7.40 (dd, 1H), 7.32 (br d, 1H), 7.13 (br t, 1H), 6.83 (br q, 1H), 6.61 (ddd, 1H), 4.32-3.94 (m, 4H), 3.92-3.84 (m, 1H), 3.82-3.71 (m, 2H), 2.56 (br, 1H), 1.94 (br, 2H), 1.26 (br, 1H); MS (EI) for C19H17F3IN5O3: 548 (MH+).

後処理

  1. extractionwas extracted twice with ethyl acetate
  2. washThe combined organic portion was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-c39cd31beb8a4bfbbeedd3fdc67521da
出典データセット
uspto-grants-2011_03
特許番号
US07915250B2

反応ノート

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