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

HRID 630301노트

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HRID 630301 반응식
[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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 313Hydrochloric Acid용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9abd60c1dbb8474583d348cdfa1dc46c
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09315509B2

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