Acetic Anhydride → HCID 59837439, compound

HRID 272978Notes

Reaction equation

HRID 272978 reaction equation
[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][N:23]4[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]4)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[C:38](OC(=O)C)(=[O:40])[CH3:39]>ClCCl>[C:38]([N:26]1[CH2:25][CH2:24][N:23]([CH2:22][C:16]2([C:13]3[CH:14]=[CH:15][C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:11][CH:12]=3)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]2)[CH2:28][CH2:27]1)(=[O:40])[CH3:39]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 59837542HCID 59837542, compound

Product 1

HCID 59837439HCID 59837439, compoundYield 19.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 1-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-ylmethyl}piperazine (160 mg, 0.41 mmol) and N,N-diisopropylethylamine (180 μl, 1.03 mmol) in dichloromethane (2 ml) at 0° C. was added dropwise acetic anhydride (47 μl, 0.49 mmol). The reaction was allowed to warm up to room temperature and stirred for 18 hours. The reaction mixture was concentrated under reduced pressure and the residue partitioned between dichloromethane (20 ml) and aqueous sodium carbonate solution (20 ml). The layers were separated and the aqueous layer was extracted again with dichloromethane (20 ml). The organics were combined, dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 90:10:1 by volume) to provide the title compound (34 mg, 19%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 1.78-1.81 (m, 4H), 1.83-1.89 (m, 2H), 1.99 (s, 3H), 2.01-2.03 (m, 2H), 2.06-2.11 (m, 3H), 2.15-2.18 (m, 3H), 2.40 (s, 2H), 2.51-2.53 (m, 4H), 2.63 (t, 2H), 3.22 (t, 2H), 3.42-3.44 (m, 2H), 3.52 (t, 2H), 3.73-3.76 (m, 2H), 4.02 (t, 2H), 6.86 (d, 2H), 7.21 (d, 2H). HRMS ESI+ m/z 430.3052 [MH]+.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe residue partitioned between dichloromethane (20 ml) and aqueous sodium carbonate solution (20 ml)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted again with dichloromethane (20 ml)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 90:10:1 by volume)

Sources & evidence

ORD record
ord-9af4673e300c431ca6c20c05c4078dd0
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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