Water → (R)-tert-butyl 2-(2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)acetate

HRID 2169555Notes

Reaction equation

HRID 2169555 reaction equation
[H-].[Na+].[Cl:3][C:4]1[N:13]=[CH:12][C:11]2[NH:10][CH2:9][C@@H:8]3[CH2:14][O:15][CH2:16][CH2:17][N:7]3[C:6]=2[N:5]=1.Br[CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].O>CN(C=O)C>[Cl:3][C:4]1[N:13]=[CH:12][C:11]2[N:10]([CH2:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:9][C@@H:8]3[CH2:14][O:15][CH2:16][CH2:17][N:7]3[C:6]=2[N:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 86670088(R)-2-chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

Product 1

HCID 86670103(R)-tert-butyl 2-(2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)acetateYield 67.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in oil, 19.41 mg, 0.485 mmol) was added to a solution of (R)-2-chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x3, 100 mg, 0.441 mmol) in DMF (1 mL) at 0° C. The resulting mixture was stirred at room temperature for 30 minutes, after which tert-butyl bromoacetate (0.078 mL, 0.529 mmol) was added at 0° C. The reaction mixture was stirred at room temperature for 30 minutes. Water was added and the mixture was extracted with EtOAc, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, 20-80% EtOAc/hexane gradient) to afford the title compound as an off-white solid (101 mg, 67.2%). 1H NMR (400 MHz, CDCl3) δ 1.44-1.49 (m, 9 H), 3.01-3.11 (m, 1 H), 3.15-3.29 (m, 2 H), 3.37 (dd, J=11.37, 8.84 Hz, 1 H), 3.58 (td, J=11.94, 2.91 Hz, 1 H), 3.64-3.76 (m, 2 H), 3.88-4.07 (m, 3 H), 4.53 (dd, J=13.89, 2.02 Hz, 1 H), 7.22 (s, 1 H). ESI-MS m/z [M+H]+ calc'd for C15H21ClN4O3, 341.13; found 341.2

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 30 minutes
  2. extractionthe mixture was extracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (SiO2, 20-80% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-fd9da485612a4e89af0ecb4fc04d60dc
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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