Potassium Carbonate → methyl 4-[[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate
Reaction equation
[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]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
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.
Workup
- additionwas added slowly enough
- extractionOnce the pH was 11, the solution was extracted with CH2Cl2 until no product
- concentrationThe combined organic fractions were concentrated under vacuum
Sources & evidence
- ORD record
- ord-9abd60c1dbb8474583d348cdfa1dc46c
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09315509B2
Reaction notes
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