Acetic Acid → HCID 90408723, compound

HRID 1855095Notes

Reaction equation

HRID 1855095 reaction equation
CC1(C)CC(O)CC(C)(C)N1[O:11][C:12]12[CH2:19][CH2:18][C:15]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH:21]=3)([CH2:16][CH2:17]1)[O:14][CH2:13]2.CC(O)=O.O>C1COCC1.[Zn]>[O:26]([C:22]1[CH:21]=[C:20]([C:15]23[CH2:18][CH2:19][C:12]([OH:11])([CH2:17][CH2:16]2)[CH2:13][O:14]3)[CH:25]=[CH:24][CH:23]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 962WaterHCID 90409086HCID 90409086, compound

Product 1

HCID 90408723HCID 90408723, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 96B [2,2,6,6-tetramethyl-1-((1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)oxy)piperidin-4-ol] (140 mg, 0.310 mmol), activated zinc dust (203 mg, 3.10 mmol), and HOAc (3.55 mL, 62.0 mmol) in THF (1 mL)/water (0.5 mL) was stirred at rt for 3 days, then was filtered. The filtrate was dissolved in EtOAc (5 mL) and washed with water. The organic layer was dried (MgSO4) and concentrated in vacuo. The crude product was chromatographed [SiO2; continuous gradient of EtOAc/hexane (0% to 50% over 10 min)] to give the title compound (62 mg, 0.209 mmol, 68% yield) as a clear oil. [M+Na]+=319.1; 1H NMR (CDCl3) δ: 7.38-7.27 (m, 3H), 7.20-7.09 (m, 3H), 7.06-6.99 (m, 2H), 6.92-6.86 (m, 1H), 3.88 (t, J=1.6 Hz, 2H), 2.24-2.12 (m, 4H), 2.01-1.84 (m, 4H), 1.70 (s, 1H).

Workup

  1. filtrationwas filtered
  2. dissolutionThe filtrate was dissolved in EtOAc (5 mL)
  3. washwashed with water
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was chromatographed [SiO2; continuous gradient of EtOAc/hexane (0% to 50% over 10 min)]

Sources & evidence

ORD record
ord-1812afcbd60043a3ba08e98f4e8e0a50
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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