Acetic Acid → HCID 11951998, compound

HRID 1669071Notes

Reaction equation

HRID 1669071 reaction equation
Cl.[CH3:2][O:3][CH:4]1[CH2:7][NH:6][CH2:5]1.[O-:8][N+:9]1[C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][C:13]=2[N:12]=[C:11]([CH2:22][CH2:23][CH:24]=O)[N:10]=1)[CH2:19][CH2:18][CH2:17]3.[BH3-]C#N.[Na+].CC(O)=O>CO>[CH3:2][O:3][CH:4]1[CH2:7][N:6]([CH2:24][CH2:23][CH2:22][C:11]2[N:10]=[N+:9]([O-:8])[C:14]3[CH:15]=[C:16]4[C:20]([CH2:19][CH2:18][CH2:17]4)=[CH:21][C:13]=3[N:12]=2)[CH2:5]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 222428583-Methoxyazetidine hydrochlorideHCID 57786560HCID 57786560, compound

Product 1

HCID 11951998HCID 11951998, compoundYield 60.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3-Azetidinyl methyl ether hydrochloride (275) (MacKenzie et al., PCT Int Appl. WO 9605193, 1996) (0.60 g, 4.9 mmol) was added to a stirred solution of propanal 75 (1.2 g, 4.9 mmol) in MeOH (100 mL) at 0° C. and the solution stirred for 30 min. NaCNBH3 (1.5 g, 24 mmol) was added and the solution stirred at 0° C. for 30 min and then HOAc (2 mL) was added and the mixture was stirred at 20° C. for 16 h. The solvent was evaporated and the residue was partitioned between DCM (200 mL) and water (200 mL). The aqueous phase was extracted with DCM (2×200 mL), the combined organic phase was dried and the solvent evaporated. The residue was purified by chromatography, eluting with 10% MeOH/EtOAc, to give 1-oxide 82 (930 mg, 60%) as a yellow oil: 1H NMR δ 8.24 (s, 1H, H-9), 7.74 (s, 1H, H-5), 4.27-4.39 (m, 3H, CH2N, CHO), 3.49-3.53 (m, 2H, CH2N), 3.30 (s, 3H, OCH3), 3.21-3.27 (m, 2H, CH2N), 3.09-3.16 (m, 4H, H-6, H-8), 3.05 (t, J=7.2 Hz, 2H, CH2), 2.14-2.26 (m, 4H, H-7, CH2); 13C NMR δ 163.9, 155.1, 149.3, 147.3, 132.3, 122.7, 144.2, 68.3, 60.9, 58.7, 56.6, 56.5, 33.5, 33.1, 32.8, 25.7, 23.8; HRMS calcd for C17H22N4O2 (M+) m/z 314.1743, found 314.1742.

Workup

  1. stirringthe solution stirred at 0° C. for 30 min
  2. stirringthe mixture was stirred at 20° C. for 16 h
  3. customThe solvent was evaporated
  4. customthe residue was partitioned between DCM (200 mL) and water (200 mL)
  5. extractionThe aqueous phase was extracted with DCM (2×200 mL)
  6. customthe combined organic phase was dried
  7. customthe solvent evaporated
  8. customThe residue was purified by chromatography
  9. washeluting with 10% MeOH/EtOAc

Sources & evidence

ORD record
ord-9e36e6761d594ce38998248533f94927
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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