tert-Butyl methyl ether → (S)-3-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

Pd(OH)2/C (1.2 g, 1.71 mmol) was flushed with argon, (S)-3-(6-Benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (10.95 g, 26.7 mmol) dissolved in methanol (25 mL) was added followed by the addition of ammonium formate (1.68 g, 26.7 mmol). The reaction mixture was refluxed for 1 h, cooled down to room temperature, filtered through a celite pad and concentrated under vacuum. Purification by flash chromatography on silica gel (CH2Cl2 then TBME then TBME/MeOH 100/0 to 90/10 then TBME/MeOH/NH4OH 85/15/5) gave (S)-3-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (7.39 g, 87% yield) as a yellow sticky oil. 1H NMR (400 MHz, methanol-d4, 298K) δ ppm 1.46-1.46 (m, 9 H) 2.10-2.30 (m, 2 H) 2.78-2.83 (m, 2 H) 3.11-3.14 (m, 2 H) 3.41-3.60 (m, 3 H) 3.65-3.72 (m, 1 H) 3.78 (s, 2 H) 5.68 (m, 1 H) 8.52 (s, 1 H). LCMS: [M+H]+=321.2, Rt(2)=0.87 min

Provenance & Evidence