3-azetidinecarboxylic Acid → HCID 67167733, compound

HRID 1506361Notes

Reaction equation

HRID 1506361 reaction equation
[CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:14]3[CH2:15][CH2:16][C:17]4[C:22]([C:13]=3[O:12][N:11]=2)=[CH:21][CH:20]=[C:19]([CH:23]=O)[CH:18]=4)=[CH:6][CH:5]=1)[CH2:2][CH3:3].[NH:25]1[CH2:28][CH:27]([C:29]([OH:31])=[O:30])[CH2:26]1.C([BH3-])#N.[Na+]>ClC(Cl)C.CO.C(O)(=O)C>[CH2:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:14]3[CH2:15][CH2:16][C:17]4[C:22]([C:13]=3[O:12][N:11]=2)=[CH:21][CH:20]=[C:19]([CH2:23][N:25]2[CH2:28][CH:27]([C:29]([OH:31])=[O:30])[CH2:26]2)[CH:18]=4)=[CH:6][CH:5]=1)[CH2:2][CH3:3]

Participants

7

Reactant 3

HCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 86669884HCID 86669884, compound

Product 1

HCID 67167733HCID 67167733, compoundYield 37.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
80 °C

Procedure

To 3-(4-propylphenyl)-4,5-dihydronaphtho[2,1-d]isoxazole-7-carbaldehyde (Preparation 20E, 0.191 g, 0.602 mmol) in dichloroethane (2 mL) and methanol (2.0 mL) was added azetidine-3-carboxylic acid (0.073 g, 0.722 mmol) and 8 drops of acetic acid. The reaction mixture was heated at 80° C. for 1.5 h. The reaction mixture was cooled to room temperature and sodium cyanoborohydride (0.045 g, 0.722 mmol) was added in one lot. The reaction mixture was stirred at room temperature for 20 min., and then concentrated. Acetonitrile (10 mL) was added to the resulting residue. The contents were sonicated for ˜2 min. and filtered. The solid was washed with acetonitrile (2×10 mL), water (2×10 mL), acetonitrile (5 mL), and dried to yield 1-((3-(4-propylphenyl)-4,5-dihydronaphtho[2,1-d]isoxazol-7-yl)methyl)azetidine-3-carboxylic acid as a grey solid (90 mgs). The compound had an HPLC retention time=3.08 min (condition C); LC/MS M+1=403.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated
  3. additionAcetonitrile (10 mL) was added to the resulting residue
  4. customThe contents were sonicated for ˜2 min.
  5. filtrationfiltered
  6. washThe solid was washed with acetonitrile (2×10 mL), water (2×10 mL), acetonitrile (5 mL)
  7. customdried

Sources & evidence

ORD record
ord-97be520599814dfaaab7b58c1040f041
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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