Acetyl chloride → HCID 57968592, compound

HRID 882763Notes

Reaction equation

HRID 882763 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([C@@H:14]3[CH2:18][C@H:17]([O:19][C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[CH2:16][NH:15]3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.CCN(CC)CC.[C:34](Cl)(=[O:36])[CH3:35]>C1COCC1.C([O-])(O)=O.[Na+]>[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([C@@H:14]3[CH2:18][C@H:17]([O:19][C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)[CH2:16][N:15]3[C:34](=[O:36])[CH3:35])=[O:13])[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 44601159HCID 44601159, compound

Product 1

HCID 57968592HCID 57968592, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (2S,4S)-2-(4-cyclobutyl-[1,4]diazepane-1-carbonyl)-4-(4-fluoro-phenoxy)-pyrrolidine (102 mg, 0.85 mmol) and Et3N (0.197 mL) in THF (2.82 mL) was added acetyl chloride (60 μL, 0.85 mmol). After 48 h, the mixture was diluted with saturated (satd.) aq. NaHCO3 and extracted with CH2Cl2 (3×). The combined organic layers were dried and evaporated. The residue was purified by FCC, followed by reverse phase HPLC (5-99% CH3CN/20 mM NH4OH) to give the desired product (69 mg, 61%). MS (ESI): mass calcd. for C22H30FN3O3, 403.23; m/z found, 404.3 [M+H]+. 1H NMR (CDCl3): 7.02-6.92 (m, 2H), 6.87-6.77 (m, 2H), 4.92-4.79 (m, 2H), 4.12-3.96 (m, 1H), 3.84-3.47 (m, 5H), 2.92-2.77 (m, 1H), 2.66-2.51 (m, 2H), 2.50-2.41 (m, 2H), 2.39-2.30 (m, 1H), 2.22-2.12 (m, 1H), 2.10 (d, J=2.1 Hz, 3H), 2.07-1.98 (m, 2H), 1.92-1.72 (m, 4H), 1.71-1.54 (m, 2H).

Workup

  1. extractionextracted with CH2Cl2 (3×)
  2. customThe combined organic layers were dried
  3. customevaporated
  4. customThe residue was purified by FCC

Sources & evidence

ORD record
ord-4fe53906cbd240dfa9d11ef140beed00
Source dataset
uspto-grants-2012_08
Patent number
US08236792B2

Reaction notes

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