Acetic Anhydride → HCID 59371301, compound

HRID 2095331Notes

Reaction equation

HRID 2095331 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[CH2:8]([O:15][C:16]([N:18]1[CH2:21][CH2:20][C@H:19]1[CH2:22][O:23][C:24]1[CH:25]=[C:26]([C:30]2[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=2)[CH2:33][NH2:34])[CH:27]=[N:28][CH:29]=1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(N(CC)CC)C>C(Cl)Cl>[CH2:8]([O:15][C:16]([N:18]1[CH2:21][CH2:20][C@H:19]1[CH2:22][O:23][C:24]1[CH:25]=[C:26]([C:30]2[CH:31]=[C:32]([CH:35]=[CH:36][CH:37]=2)[CH2:33][NH:34][C:1](=[O:3])[CH3:2])[CH:27]=[N:28][CH:29]=1)=[O:17])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 59371494HCID 59371494, compound

Product 1

HCID 59371301HCID 59371301, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 15 mL round-bottom flask with magnetic stirrer, septum, and balloon (for pressure equalization and exclusion of moisture), neat acetic anhydride (23 μL, 0.24 mmol, 1.5 equiv.) was added with ice cooling in 5 min to a solution of 3-[5-[[1-(benzyloxycarbonyl)-2(S)-azetidinyl]methoxy]-3-pyridyl]benzylamine (65.3 mg, 162 μmol) and triethylamine (45 μL, 0.32 mmol, 2 equiv.) in anhydrous CH2Cl2 (1 mL). Stirring was continued at room temperature for 85 min, while the septum was replaced with a glass stopper to avoid evaporation losses. After 65 min, TLC (SiO2, CH2Cl2/MeOH 9:1, UV detection) demostrated complete conversion of the starting material (Rf approx. 0.05) to the acetamide (Rf approx. 0.45). Methanol (25 μL) was added, and the reaction mixture was stored at room temperature for 1 h before being directly applied on a SiO2 column (26×1.3 cm; eluent: CH2Cl2/MeOH 94:6 for a forerun, then 9:1). The product-containing fractions were evaporated and dried (50° C./oil pump) to yield 69.1 mg (96%) of the amide as a colorless glass. [α]D−40.7, [α]546−48.3 (c 14.8 g/L, EtOAc). 1H NMR (CDCl3, 500 MHz) δ 8.47 (s, 1H), 8.32 (br, 1H), 7.55-7.48 (m, 2H), 7.47 (t, 1H, J=7.5 Hz), approx. 7.4 (br and overlapping, 1H), 7.30 (d, 1H, J=7.4 Hz), 7.31 (br s, 5H), 5.89 (br, 1H), 5.12, 5.07 (ABq, 2H, J=12.3 Hz), 4.67 (br, 1H), 4.54 (d, 2H, J=5.7 Hz), approx. 4.4-4.5 (br, 1H), 4.22 (br, 1H), 4.09-4.00 (m, 2H), 2.51-2.32 (m, 2H), 2.08 (s, 3H). MS (EI) m/z 445 (M+, 8.46%), 354 (2.2%), 312 (2.8%), 310 (5.9%), 242 (6.5%), 199 (5.0%), 91 (100%), 43 (11%).

Workup

  1. customevaporation losses
  2. waitAfter 65 min
  3. additionMethanol (25 μL) was added
  4. waitthe reaction mixture was stored at room temperature for 1 h
  5. customThe product-containing fractions were evaporated
  6. customdried (50° C./oil pump)

Sources & evidence

ORD record
ord-937dd38354b44c208aa0ab7889ad837b
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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