Allyl bromide → tert-butyl ((5RS,6SR)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate

HRID 627596ノート

反応式

HRID 627596 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[C:11]1([CH3:29])[CH2:16][S:15](=[O:18])(=[O:17])[C:14]([CH3:20])([CH3:19])[C:13]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[N:12]1.[CH:30]([N-]C(C)C)([CH3:32])[CH3:31].[Li+].C(Br)C=C>C1COCC1.O1CCCC1.CCCCCCC.C(C1C=CC=CC=1)C>[CH2:32]([CH:16]1[S:15](=[O:18])(=[O:17])[C:14]([CH3:20])([CH3:19])[C:13]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[N:12][C:11]1([C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[F:1])[CH3:29])[CH:30]=[CH2:31]

参加物

6

反応物 3

HCID 7841Allyl bromideHCID 2724682Lithium diisopropylamideHCID 86728095tert-butyl (5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate

生成物 1

HCID 86728096tert-butyl ((5RS,6SR)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate収率 7.9%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 22742125Tetrahydrofuran heptane ethylbenzol溶媒

反応条件

温度
-78 °C

実験手順

To a solution of tert-butyl (5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (230 mg, 0.536 mmol) in THF (5 ml) was added lithium diisopropylamide, (2.0 M solution in tetrahydrofuran/heptane/ethylbenzene) (0.803 ml, 1.607 mmol) dropwise at −78° C. and the mixture was stirred for 20 min at the −78° C. To a resulting dark solution, allyl bromide (0.139 ml, 1.607 mmol) was added dropwise and the mixture was stirred for another 20 min. The reaction was quenched with NH4Cl solution at −78° C., the flask was removed from the bath and allowed to reach RT. The mixture was extracted with ethyl acetate, organic layer was washed with brine, concentrated and the concentrated crude residue was separated on 12 g RediSep Gold column using 5-50% EtOAc in heptane solvent gradient to afford tert-butyl ((5RS,6RS)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (120 mg, 0.256 mmol, 47.7% yield) as major diastereomer and tert-butyl ((5RS,6SR)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (20 mg, 0.043 mmol, 7.9% yield) as minor diastereomer.

後処理

  1. stirringthe mixture was stirred for another 20 min
  2. customThe reaction was quenched with NH4Cl solution at −78° C.
  3. customthe flask was removed from the bath
  4. customto reach RT
  5. extractionThe mixture was extracted with ethyl acetate, organic layer
  6. washwas washed with brine
  7. concentrationconcentrated
  8. concentrationthe concentrated crude residue
  9. customwas separated on 12 g RediSep Gold column

出典と根拠

ORDレコード
ord-5606900a03464e7c86bfc9be62b378ac
出典データセット
uspto-grants-2016_04
特許番号
US09309263B2

反応ノート

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