Oxalyl chloride → N-methoxy-N-methyl-3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-6-ene-7-carboxamide

HRID 218066

反応式

HRID 218066 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[CH:10]([CH2:11][C:12]([C:16]([OH:18])=O)=[CH:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C.Cl.[CH3:35][NH:36][O:37][CH3:38]>ClCCl.CN(C=O)C>[CH3:38][O:37][N:36]([CH3:35])[C:16]([C:12]1[CH2:11][CH:10]2[CH:14]([CH2:15][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]2)[CH:13]=1)=[O:18]

参加物

7

反応物 4

HCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 684690633-(Tert-butoxycarbonyl)-3-azabicyclo[3.3.0]-oct-6-ene-7-carboxylic acid

生成物 1

HCID 86643297N-methoxy-N-methyl-3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-6-ene-7-carboxamide収率 82.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]-oct-6-ene-7-carboxylic acid (0.080 g, 0.32 mmol) in dichloromethane (3.0 mL) was added oxalyl chloride (0.20 g, 1.6 mmol), followed by a drop of DMF. After stirring for 1 h, the the reaction mixture was concentrated in vacuo, and the residual acid chloride was dissolved in acetonitrile (3.0 mL). DIPEA (0.17 mL, 0.96 mmol) and N,O-dimethylhydroxylamine hydrochloride (0.042 g, 0.43 mmol) were added, and the reaction was stirred at ambient temperature for 1 h. The solvent was evaporated, and the residue was purified by silica gel column chromatography, eluting with 80-90% ethyl acetate in hexanes, to obtain 0.078 g (82% yield) of N-methoxy-N-methyl-3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]oct-6-ene-7-carboxamide, as an oil. This was dissolved in dichloromethane (3.0 mL), treated with TFA (2.0 mL) and stirred at ambient temperature for 1 h. The volatiles were evaporated, and the residue was vacuum dried to obtain 0.07 g of N-methoxy-N-methyl-3-azabicyclo[3.3.0]oct-6-ene-7-carboxamide trifluoroacetate, as an oil (1H NMR (CD3OD, 300 MHz): δ 6.29 (bs, 1H), 3.80-3.89 (m, 1H), 3.88 (s, 3H), 3.54-3.41 (m, 2H), 3.38-3.30 (m, 1H), 3.26 (s, 3H), 3.22-3.03 (m, 3H), 2.66-2.59 (m, 1H); MS (m/z): 197 (M+1)).

後処理

  1. concentrationthe the reaction mixture was concentrated in vacuo
  2. dissolutionthe residual acid chloride was dissolved in acetonitrile (3.0 mL)
  3. stirringthe reaction was stirred at ambient temperature for 1 h
  4. customThe solvent was evaporated
  5. customthe residue was purified by silica gel column chromatography
  6. washeluting with 80-90% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-fbc062b2b7a0482cbf9bfd4c2a61d678
出典データセット
uspto-grants-2012_06
特許番号
US08198296B2

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