tert-Butyl hydroperoxide → [5-(3-Bromo-phenyl)-6-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

HRID 81528ノート

反応式

HRID 81528 の反応式
BrC1C=C(C2([CH2:15][F:16])NC(=S)COC2)C=CC=1.C(OO)(C)(C)C.[NH4+].[OH-].[Br:25][C:26]1[CH:27]=[C:28]([C:32]2(CF)[CH2:37][O:36][CH2:35][C:34]([NH2:38])=[N:33]2)[CH:29]=[CH:30][CH:31]=1.CCN(C(C)C)C(C)C.[CH3:50][C:51]([O:54][C:55]([O:57]C(OC(C)(C)C)=O)=O)([CH3:53])[CH3:52]>N.CO.ClCCl>[C:51]([O:54][C:55](=[O:57])[NH:38][C:34]1[CH2:35][O:36][CH:37]([CH2:15][F:16])[CH:32]([C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([Br:25])[CH:27]=2)[N:33]=1)([CH3:53])([CH3:52])[CH3:50]

参加物

9

反応物 6

HCID 6410tert-Butyl hydroperoxideHCID 14923Ammonium HydroxideHCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 66666031HCID 66666031、化合物HCID 86650251HCID 86650251、化合物

生成物 1

HCID 86716529[5-(3-Bromo-phenyl)-6-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 21705897Ammonia methanol溶媒

実験手順

To a solution of 5-(3-bromo-phenyl)-5-fluoromethyl-morpholine-3-thione (200 mg, 0.658 mmol) in 5 ml of 7M NH3/MeOH were added t-butyl hydroperoxide (80%, 0.818 ml, 6.58 mmol) and then 1.7 ml of 25% aqueous NH4OH. After 2 h, the mixture was quenched with a saturated aqueous solution of Na2S2O3 and extracted with EtOAc. The extract was washed with brine, dried with sodium sulfate and evaporated. The crude 5-(3-bromo-phenyl)-5-fluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine (189 mg, 0.658 mmol) was dissolved in 4 ml of dichloromethane. The solution was treated with DIPEA (0.172 ml, 0.987 mmol) and Boc2O (187 mg, 0.855 mmol). After 14 h, the mixture was diluted with dichloromethane and washed with water, 1N HCl and brine. The organic phase was dried with sodium sulfate and evaporated. The residue was chromatographed on silica gel (cyclohexane/EtOAc=6:1) to yield the title compound. TLC (hexane/EtOAc=6:1): Rf=0.20; HPLC: RtH1=2.380 min; 1H-NMR (400 MHz, CDCl3): 7.56-6.98 (m, 4H; broad signals due to rotamers), 4.80-3.60 (m, 6H), 1.42 (br, 9H); MS: 387, 389 [(M+H)+].

後処理

  1. customthe mixture was quenched with a saturated aqueous solution of Na2S2O3
  2. extractionextracted with EtOAc
  3. washThe extract was washed with brine
  4. dry with materialdried with sodium sulfate
  5. customevaporated
  6. waitAfter 14 h
  7. washwashed with water, 1N HCl and brine
  8. dry with materialThe organic phase was dried with sodium sulfate
  9. customevaporated
  10. customThe residue was chromatographed on silica gel (cyclohexane/EtOAc=6:1)

出典と根拠

ORDレコード
ord-6de07e70ae984ff7bb1841da8eab8814
出典データセット
uspto-grants-2014_09
特許番号
US08846658B2

反応ノート

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