Acetic Acid → HCID 67264537, compound

HRID 1041183Notes

Reaction equation

HRID 1041183 reaction equation
Br[C:2]1[C:12]2[CH2:11][CH2:10][C:9](=O)[CH2:8][CH2:7][C:6]=2[C:5]([O:14][CH3:15])=[C:4]([N+:16]([O-:18])=[O:17])[CH:3]=1.[NH:19]1[CH2:24][CH2:23][CH2:22][CH:21]([OH:25])[CH2:20]1.C(Cl)Cl.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH3:15][O:14][C:5]1[C:6]2[CH2:7][CH2:8][CH:9]([N:19]3[CH2:24][CH2:23][CH2:22][CH:21]([OH:25])[CH2:20]3)[CH2:10][CH2:11][C:12]=2[CH:2]=[CH:3][C:4]=1[N+:16]([O-:18])=[O:17]

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 232933-HydroxypiperidineHCID 5049666Sodium triacetoxyborohydrideHCID 57522509HCID 57522509, compound

Product 1

HCID 67264537HCID 67264537, compound

Conditions

Temperature
40 °C

Procedure

To a stirred solution of 4-bromo-1-methoxy-2-nitro-5,6,8,9-tetrahydro-benzocyclohepten-7-one (2.00 g, 0.00637 mol) and piperidin-3-ol (6 g, 0.06 mol) in methylene chloride (100 mL, 2 mol) at room temperature was added acetic acid (4 mL, 0.06 mol) dropwise. Molecular sieves (2 mass equiv) were added to the reaction mixture and the contents heated at 40° C. overnight. The reaction mixture was cooled to room temperature then at 0° C. in an ice bath. Sodium triacetoxyborohydride (7 g, 0.03 mol) was added in one portion as a solid. The reaction mixture continued to stirr at 0° C. for 1 h then warmed to room temperature for 4 h Workup involved quenching with water, adjusting the pH to 8-10 with 10 N NaOH (aq) and extracting with methylene chloride. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo to a dark oil. Purification involved ISCO chromatography on silica gel (40 g column) using methylene chloride-methanol with 5% ammonium hydroxide. Fractions corresponding to product (polar fractions) were combined and concentration to give 1-(1-methoxy-2-nitro-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl)-piperidin-3-ol as a brown oil. 1H NMR (400 MHz, CDCl3) δ 7.94 (s, 1H), 3.86 (s, 4H), 3.47 (m, 3H), 2.88 (t, 1H, J=11 Hz), 2.60-2.70 (m, 4H), 2.48-2.41 (m, 2H), 2.21 (m, 2H), 1.86 (m, 2H), 1.59 (m, 3H), 1.26-1.39 (m, 2H).

Workup

  1. additionMolecular sieves (2 mass equiv) were added to the reaction mixture
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customat 0° C.
  4. temperaturethen warmed to room temperature for 4 h Workup
  5. custominvolved quenching with water
  6. extractionextracting with methylene chloride
  7. dry with materialThe organic phase was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo to a dark oil
  10. customPurification
  11. concentrationconcentration

Sources & evidence

ORD record
ord-38717ff95cd442c290deddbc930561bc
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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