Potassium Carbonate → methyl 4-[[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate

HRID 630301ノート

反応式

HRID 630301 の反応式
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[CH2:17][C@@H:16]3[CH2:18][C@H:13]2[CH2:14][N:15]3C(OC(C)(C)C)=O)=[CH:7][CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+]>Cl>[C@H:13]12[CH2:18][C@H:16]([NH:15][CH2:14]1)[CH2:17][N:12]2[CH2:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=1

参加物

4

反応物 2

HCID 11430Potassium CarbonateHCID 71213169tert-Butyl (1S,4S)-5-(4-(methoxycarbonyl)benzyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

生成物 1

HCID 68488731methyl 4-[[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate収率 97%

試薬・触媒・溶媒 1

HCID 313Hydrochloric Acid溶媒

実験手順

1,1-Dimethylethyl (1S,4S)-5-[[4-(methoxycarbonyl)phenyl]methyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (44.1 g, 127.3 mmol) was slurried in HCl (2 M in water, 0.6 L). The solid went into solution over 2 hours, and the solution was stirred for another 16 hours. The reaction was cooled to −5 C and saturated K2CO3 was added slowly enough to keep the temperature below 0 C to prevent ester hydrolysis. Once the pH was 11, the solution was extracted with CH2Cl2 until no product was observed in the water layer by TLC (3×). The combined organic fractions were concentrated under vacuum to obtain pure methyl 4-[[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate (30.3 g, 97%) as the freebase; 1H NMR (CD3OD) δ 7.98 (d, 2H), 7.49 (d, 2H), 4.00 (sbr, 1H), 3.90 (s, 3H), 3.88 (d, 1H), 3.80 (d, 1H), 3.57 (sbr, 1H), 3.39 (ddbr, 1H), 3.03 (ddbr, 1H), 2.88 (ddbr, 1H), 2.72 (ddbr, 1H), 2.09 (dbr, 1H), 1.75 (dbr, 1H) ppm.

後処理

  1. additionwas added slowly enough
  2. extractionOnce the pH was 11, the solution was extracted with CH2Cl2 until no product
  3. concentrationThe combined organic fractions were concentrated under vacuum

出典と根拠

ORDレコード
ord-9abd60c1dbb8474583d348cdfa1dc46c
出典データセット
uspto-grants-2016_04
特許番号
US09315509B2

反応ノート

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