Sodium Hydroxide → (R)-2-Hydroxy-1-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-9-yl]-azetidin-1-yl}-propan-1-one

HRID 1849320Notes

Reaction equation

HRID 1849320 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[CH:6]=[CH:7][C:8]3[O:17][CH2:16][CH2:15][C:14]4[S:13][C:12]([C:18]5[N:19]([CH:23]([CH3:25])[CH3:24])[N:20]=[CH:21][N:22]=5)=[N:11][C:10]=4[C:9]=3[CH:26]=2)[CH2:2]1.[C:27]([O-])(=[O:31])[C@@H:28]([CH3:30])[OH:29].[Na+].[OH-].[Na+]>CN(C=O)C.O1CCOCC1.CCOC(C)=O.O>[OH:29][C@H:28]([CH3:30])[C:27]([N:1]1[CH2:4][CH:3]([C:5]2[CH:6]=[CH:7][C:8]3[O:17][CH2:16][CH2:15][C:14]4[S:13][C:12]([C:18]5[N:19]([CH:23]([CH3:24])[CH3:25])[N:20]=[CH:21][N:22]=5)=[N:11][C:10]=4[C:9]=3[CH:26]=2)[CH2:2]1)=[O:31]

Participants

8

Reactant 3

HCID 14798Sodium HydroxideHCID 23666457Sodium Lactate, D-HCID 670505299-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

Product 1

HCID 58204165(R)-2-Hydroxy-1-{3-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-9-yl]-azetidin-1-yl}-propan-1-oneYield 36%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Following the procedure for 318, 9-azetidin-3-yl-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene and sodium D-lactate in DMF were reacted. After purification by flash chromatography a lactate-ester by-product of the title compound was present. The mixture (0.11 g, 0.2 mmol) was dissolved in 1,4-dioxan (2 mL) and treated with 1M aqueous sodium hydroxide solution (0.2 mL, 0.2 mmol). The reaction mixture was stirred for 2 hours then diluted with EtOAc and water. The aqueous phase was extracted with EtOAc (×2) and the combined organic extracts were dried (Na2SO4) and concentrated in vacuo. Further drying under vacuum gave 398 (90 mg, 36%). LCMS: RT=10.71 min, [M+H]+=440. 1H NMR δ (ppm) (CDCl3): 8.37 (1 H, s), 7.90 (1 H, s), 7.20-7.12 (1 H, m), 7.06 (1 H, dd, J=8.28, 5.28 Hz), 5.85-5.76 (1 H, m), 4.64-4.30 (4 H, m), 4.25-4.10 (3 H, m), 3.98-3.87 (1 H, m), 3.45-3.35 (2 H, m), 1.62 (6 H, d, J=6.65 Hz), 1.33 (3 H, dd, J=11.04, 6.67 Hz). 1 Exchangeable not observed

Workup

  1. customwere reacted
  2. customAfter purification by flash chromatography a lactate-ester by-product of the title compound
  3. extractionThe aqueous phase was extracted with EtOAc (×2)
  4. dry with materialthe combined organic extracts were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customFurther drying under vacuum

Sources & evidence

ORD record
ord-85ac84f7f23f48b38daa6ede817de171
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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