Hydrochloric Acid → (R)-2-(6-(5-amino-1,3,4-thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetic acid

HRID 1798298ノート

反応式

HRID 1798298 の反応式
[NH2:1][C:2]1[S:6][C:5]([O:7][C:8]2[CH:9]=[C:10]([CH3:24])[C:11]3[C@@H:15]([CH2:16][C:17]([O:19]CC)=[O:18])[O:14][B:13]([OH:22])[C:12]=3[CH:23]=2)=[N:4][N:3]=1.C1COCC1.O[Li].O.Cl>O.CO>[NH2:1][C:2]1[S:6][C:5]([O:7][C:8]2[CH:9]=[C:10]([CH3:24])[C:11]3[C@@H:15]([CH2:16][C:17]([OH:19])=[O:18])[O:14][B:13]([OH:22])[C:12]=3[CH:23]=2)=[N:4][N:3]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 58292701(R)-ethyl 2-(6-(5-amino-1,3,4-thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate

生成物 1

HCID 58292564(R)-2-(6-(5-amino-1,3,4-thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetic acid収率 76%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 962Water溶媒

実験手順

To a solution (R)-ethyl 2-(6-(5-amino-1,3,4-thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate (30 g, 86 mmol) in a mixed solution of THF (750 mL) and methanol (100 mL) was added a solution of LiOH.H2O (12.63 g, 301 mmol) in water (750 mL) at 0° C. The resulting mixture was stirred at room temperature for 2 hrs and then acidified to pH=2 with diluted hydrochloric acid at 0° C. After removal of the volatile organics, the residue was dissolved in EtOAc. The aqueous phase was separated and concentrated in vacuo, and the residue was neutralized to pH=6.5˜7.0 using saturated aq. sodium bicarbonate. The precipitated solid was filtered and stirred with EtOAc for 1 hr. The solid was filtered, washed with cold EtOAc and water then dried to give the product (R)-2-(6-(5-amino-1,3,4-thiadiazol-2-yloxy)-1-hydroxy-4-methyl-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetic acid (21 g, 76% yield). 1H NMR (400 MHz, DMSO-d6) δ12.31 (1H, s), 9.26 (1H, s), 7.33 (1H, m), 7.16 (1H, m), 7.06 (2H, s), 5.50 (1H, m), 3.03 (1H, m), 2.29 (3H, s), 2.10 (1H, m). ESI-MS m/z 322 (M+H+, positive); [α]25D=−91.395°±0.305° (C=1.0017 g/100 ml diluted with 2M HCl, L=0.5 dm).

後処理

  1. customAfter removal of the volatile organics, the residue
  2. dissolutionwas dissolved in EtOAc
  3. customThe aqueous phase was separated
  4. concentrationconcentrated in vacuo
  5. filtrationThe precipitated solid was filtered
  6. stirringstirred with EtOAc for 1 hr
  7. filtrationThe solid was filtered
  8. washwashed with cold EtOAc and water
  9. customthen dried

出典と根拠

ORDレコード
ord-85349c80c31449cdab874cd3e78e3bbe
出典データセット
uspto-grants-2013_01
特許番号
US08343944B2

反応ノート

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