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

HRID 242306Notes

Reaction equation

HRID 242306 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([OH:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:14]([N:21]1[CH2:31][CH2:30][C:24]2[N:25]=[CH:26][N:27]=[C:28](Cl)[C:23]=2[CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][C:28]2[C:23]3[CH2:22][N:21]([CH2:14][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[CH2:31][CH2:30][C:24]=3[N:25]=[CH:26][N:27]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 854055tert-Butyl (3S)-3-hydroxypyrrolidine-1-carboxylateHCID 253240466-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido(4,3-d)pyrimidine

Product 1

HCID 57495302(S)-3-(6-Benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 85.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-3-hydroxypyrrolidine-1-carboxylic acid tert-butyl ester (0.94 g, 5.01 mmol) in THF (20 mL) was added under argon NaH (0.23 g, 5.78 mmol). The mixture was stirred at rt for 25 min., then 6-benzyl-4-chloro-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (1 g, 3.85 mmol) was added and stirring continued at rt for 4 h. The mixture was quenched with H2O, extracted with CH2Cl2. The organic layer was filtered and evaporated to dryness. Purification by flash chromatography on silica gel (heptanes/ethyl acetate, 1/1) gave the (S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.35 g, 85% yield) as a yellow gum. 1H NMR (400 MHz, DMSO-d6, 298K) δ ppm 1.39 (s, 9 H) 2.00-2.20 (m, 2 H) 2.35-2.81 (m, 4 H) 3.36-3.63 (m, 6 H) 3.70 (br.s, 2 H) 5.50-5.59 (m, 1 H) 7.25-7.37 (m, 5 H) 8.56 (s, 1 H). LCMS: [M+H]+=411.6, Rt(7)=1.00 min

Workup

  1. stirringstirring
  2. waitcontinued at rt for 4 h
  3. customThe mixture was quenched with H2O
  4. extractionextracted with CH2Cl2
  5. filtrationThe organic layer was filtered
  6. customevaporated to dryness
  7. customPurification by flash chromatography on silica gel (heptanes/ethyl acetate, 1/1)

Sources & evidence

ORD record
ord-847c899b8aa44b618726be4291cbccad
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Reaction notes

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