3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → tert-butyl 3-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylene)azetidine-1-carboxylate

HRID 1923226Notes

Reaction equation

HRID 1923226 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12]P(=O)(OC)OC)[N:8]2[CH3:11])=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[N:3]=1.[Li+].CC([N-]C(C)C)C.[C:33]([N:40]1[CH2:43][C:42](=O)[CH2:41]1)([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34]>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:12]=[C:42]3[CH2:41][N:40]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:43]3)[N:8]2[CH3:11])=[C:4]([N:19]2[CH2:20][CH2:21][O:22][CH2:23][CH2:24]2)[N:3]=1

Participants

5

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 2724682Lithium diisopropylamideHCID 59605250dimethyl (2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylphosphonate

Product 1

HCID 59605709tert-butyl 3-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylene)azetidine-1-carboxylateYield 94.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a cold (−78° C.) suspension of dimethyl (2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylphosphonate (1.1 g, 2.9 mmol) in THF (26 mL) was added a 2.0M solution of LDA in THF (1.6 mL) The resulting solution was allowed to warm to room temperature before the addition of a solution of 1-Boc-3-azetidinone (0.58 g, 3 4 mmol) in THF (12 mL). The reaction mixture was stirred at room temperature for 2 hours and partitioned between brine and DCM. The organic layer was isolated, washed with brine, dried over MgSO4 and concentrated. The crude residue was then purified by flash chromatography (0-100% EtOAc in heptane) to give the title compound (1.15 g, 93%). LCMS m/z: 421.3 (MH+).

Workup

  1. custompartitioned between brine and DCM
  2. customThe organic layer was isolated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe crude residue was then purified by flash chromatography (0-100% EtOAc in heptane)

Sources & evidence

ORD record
ord-33b89f7e2a2c4de7a767aa8388832e0b
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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