1,3,4-Thiadiazole-3(2H)-carboxaldehyde, 5-methyl-2-thioxo- → (2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid

HRID 1366376Notes

Reaction equation

HRID 1366376 reaction equation
[CH:1]1([CH2:6][C@H:7]([CH2:11][NH:12][O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[C:8]([OH:10])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.CC1SC(=S)N([CH:27]=[O:28])N=1>CC(C)=O>[CH:1]1([CH2:6][C@H:7]([CH2:11][N:12]([CH:27]=[O:28])[O:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][O:15]2)[C:8]([OH:10])=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 134681851,3,4-Thiadiazole-3(2H)-carboxaldehyde, 5-methyl-2-thioxo-HCID 86636913(2R)-3-cyclopentyl-2-{[(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid

Product 1

HCID 57937086(2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acidYield 115.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of (2R)-3-cyclopentyl-2-{[(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid (97.05 g, 358 mmol) in acetone (1.1 L) at room temperature was added 5-methyl-2-thioxo-[1,3,4]thiadiazole-3-carbaldehyde (57.3 g, 358 mmol) (Tetrahedron Lett. 1985, 26, 3703-3706). When the reaction was deemed complete, the acetone was removed in vacuo. The residue was suspended in a mixture of hexanes (320 mL) and methyl-t-butyl ether (180 mL), then sonicated. After 10 min, the white solid (presumably 5-methyl-3H-[1,3,4]thiadiazole-2-thione) was filtered off, and the filtrate was evaporated in vacuo to give (2R)-3-cyclopentyl-2-{[formyl(tetrahydro-2H-pyran-2-yloxy)amino]methyl}propanoic acid as a pale yellow gum (124 g, >100%). NMR shows the product contains a small amount of MTBE and 5-methyl-3H-[1,3,4]thiadiazole-2-thione.

Workup

  1. customthe acetone was removed in vacuo
  2. additionThe residue was suspended in a mixture of hexanes (320 mL) and methyl-t-butyl ether (180 mL)
  3. customsonicated
  4. filtrationthe white solid (presumably 5-methyl-3H-[1,3,4]thiadiazole-2-thione) was filtered off
  5. customthe filtrate was evaporated in vacuo

Sources & evidence

ORD record
ord-72ecc706be2747c0a798447be38a2eff
Source dataset
uspto-grants-2011_02
Patent number
US07893056B2

Reaction notes

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