2-Bromopropanedial → (S)-ter-Butyl 1-(5-formylthiazol-2-yl)pyrrolidine-2-carboxylate

HRID 1755471Notes

Reaction equation

HRID 1755471 reaction equation
[C:1]([N:4]1[CH2:8][CH2:7][CH2:6][C@H:5]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])(=[S:3])[NH2:2].C([O-])(=O)C.[Na+].Br[CH:22]([CH:25]=O)[CH:23]=[O:24]>C1COCC1.C(O)(=O)C>[CH:23]([C:22]1[S:3][C:1]([N:4]2[CH2:8][CH2:7][CH2:6][C@H:5]2[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[N:2][CH:25]=1)=[O:24]

Participants

6

Reactant 3

HCID 749452-BromopropanedialHCID 517045Sodium AcetateHCID 86700117(S)-tert-Butyl 1-carbamothioylpyrrolidine-2-carboxylate

Product 1

HCID 131733675(S)-ter-Butyl 1-(5-formylthiazol-2-yl)pyrrolidine-2-carboxylateYield 71.7%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of material from Example 78 (1.075 g, 4.67 mmol) in a mixture of THF (51.3 mL) and acetic acid (8.55 mL) is added sodium acetate (0.46 g, 5.60 mmol), followed by 2-bromomalonaldehyde (0.82 g, 5.13 mmol) and the reaction is stirred at room temp for 2 h. The solvent is removed in vacuo, the residue is partitioned between water and CH2Cl2 and the water layer is extracted with CH2Cl2 (1×20 mL). The organic layers are combined, partitioned with water and treated with solid sodium bicarbonate until the water layer has pH=8. The water layer is extracted with CH2Cl2 (2×25 mL), the organic layers are combined, washed with brine, dried over MgSO4, filtered and the solvent is removed in vacuo, The resulting residue is purified by BIOTAGE® Silica gel chromatography on a Thompson Single Step silica cartridge using an isocratic mixture of 40% ethyl acetate/60% CH2Cl2 to give 945 mg (68.1%) of the title compound as a yellow solid. LC/MS (Condition A): ret. T=3.23 min, (M+Na) 305.14. 1H NMR (400 MHz, chloroform-d) δ ppm 9.69 (1 H, s), 7.89 (1 H, s), 4.49 (1 H, br. s.), 3.36-3.87 (2 H, m), 2.32-2.51 (1 H, m), 2.03-2.29 (3 H, m), 1.46 (9 H, s).

Workup

  1. customThe solvent is removed in vacuo
  2. customthe residue is partitioned between water and CH2Cl2
  3. extractionthe water layer is extracted with CH2Cl2 (1×20 mL)
  4. custompartitioned with water
  5. additiontreated with solid sodium bicarbonate until the water layer
  6. extractionThe water layer is extracted with CH2Cl2 (2×25 mL)
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customthe solvent is removed in vacuo
  11. customThe resulting residue is purified by BIOTAGE® Silica gel chromatography on a Thompson Single Step silica cartridge
  12. additionan isocratic mixture of 40% ethyl acetate/60% CH2Cl2

Sources & evidence

ORD record
ord-5d2d894c3c2f4c8986f1db37628935cf
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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