Triethylamine → {4-[(2R,3R)-3-{[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid

HRID 603927ノート

反応式

HRID 603927 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13]SC3C([N+]([O-])=O)=CC=CN=3)[C@H:9]2[C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([O:32]C(C)(C)C)=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.Br[CH2:66][C:67]([C:69]1[CH:78]=[CH:77][C:72]2[O:73][CH2:74][CH2:75][O:76][C:71]=2[CH:70]=1)=[O:68]>CC(C)=O.O>[O:73]1[C:72]2[CH:77]=[CH:78][C:69]([C:67](=[O:68])[CH2:66][S:13][C@H:10]3[C:11](=[O:12])[N:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[C@@H:9]3[C:24]3[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([OH:32])=[O:31])=[CH:26][CH:25]=3)=[CH:70][C:71]=2[O:76][CH2:75][CH2:74]1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 27761712-Bromo-1-(2,3-dihydro-1,4-benzodioxin-6-yl)ethan-1-oneHCID 86639220{4-[(2R,3R)-1-(4-fluoro-phenyl)-3-(3-nitro-pyridin-2-yldisulfanyl)-4-oxo-azetidin-2-yl]-phenoxy}-acetic acid tert-butyl ester

生成物 1

HCID 67271262{4-[(2R,3R)-3-{[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid

試薬・触媒・溶媒 2

HCID 180Acetone溶媒HCID 962Water溶媒

実験手順

To a solution of tert-butyl (4-{(2R,3R)-1-(4-fluorophenyl)-3-[(3-nitropyridin-2-yl)dithio]-4-oxoazetidin-2-yl}phenoxy)acetate (0.100 g, 0.179 mmol) in acetone (2 ml) and water (0.5 ml) was added triphenylphosphine (0.047 g, 0.179 mmol). After 30 minutes, the mixture was concentrated. To the residue was added dichloromethane (3 ml) followed by the addition of triethylamine (0.073 g, 0.717 mmol) and 2-bromo-1-(2,3-dihydro-1,4-benzodioxin-6-yl)ethanone (0.115 g, 0.448 mmol). After 30 minutes, full conversion of the thiol had been achieved. The mixture was concentrated and to the residue was added formic acid (2 g) and trifluoroacetic acid (0.2 g). The mixture was allowed to stir at room temperature for 3 h. The crude product obtained was purified through preparative HPLC using an eluent of 10-50% CH3CN in 0.1M NH4OAc buffer. Freeze drying of pure fractions afforded the desired compound. 1H NMR [(CD3)2SO), 400 MHz] δ 4.21-4.32 (m, 9H), 5.09 (d, 1H), 6.78-7.44 (m, 11H).

後処理

  1. concentrationthe mixture was concentrated
  2. additionTo the residue was added dichloromethane (3 ml)
  3. waitAfter 30 minutes
  4. concentrationThe mixture was concentrated and to the residue
  5. additionwas added formic acid (2 g) and trifluoroacetic acid (0.2 g)
  6. customThe crude product obtained
  7. customwas purified through preparative HPLC
  8. customFreeze drying of pure fractions

出典と根拠

ORDレコード
ord-6fef6ed711de4911a3341a6879c58e2e
出典データセット
uspto-grants-2011_03
特許番号
US07906502B2

反応ノート

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