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 1798298노트

반응식

HRID 1798298 반응식
[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

참가 물질

7

반응물 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

생성물 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 acid수율 76%

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-85349c80c31449cdab874cd3e78e3bbe
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08343944B2

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