Triethylamine → HCID 58974989, compound

HRID 737060Notes

Reaction equation

HRID 737060 reaction equation
C(O[C:6]([N:8]1[CH2:11][CH:10]([C:12]([OH:14])=O)[CH2:9]1)=[O:7])(C)(C)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:21]1([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]([S:36]([C:39]3[CH:47]=[CH:46][C:42](C(O)=O)=[CH:41][CH:40]=3)(=[O:38])=[O:37])[CH:28]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.N1CC(CO)C1.C(N(CC)CC)C.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C1COCC1.ClCCl>[OH:14][CH2:12][CH:10]1[CH2:9][N:8]([C:6]([C:42]2[CH:41]=[CH:40][C:39]([S:36]([N:29]3[C:30]4[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=4)[C:27]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[CH:28]3)(=[O:38])=[O:37])=[CH:47][CH:46]=2)=[O:7])[CH2:11]1

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 124335Benzotriazol-1-yloxy-tris(dimethylamino)phosphoniumHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 13400658(Azetidin-3-yl)methanolHCID 21226445Aluminium lithium hydrideHCID 589751414-(3-Phenyl-indole-1-sulfonyl)-benzoic acid

Product 1

HCID 58974989HCID 58974989, compoundYield 35.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve azetidine-1,3-dicarboxylic acid mono-tert-butyl ester (300 mg, 1.50 mmol.) in THF (5.0 mL) and treat with lithium aluminum hydride (1.0M in ether, 3.0 mL, 3.0 mmol). Stir for 18 hours, quench with 3.0 mL of 1.0M NaOH, dilute with ether, filter through celite and evaporate. Treat the resulting 3-hydroxymethyl-azetidine-1-carboxylic acid tert-butyl ester with 10 mL of trifluoroacetic acid for 20 minutes an evaporate. Use this material without further purification. Combine 4-(3-Phenyl-indole-1-sulfonyl)-benzoic acid (100 mg, 0.26 mmol) and the resulting azetidin-3-yl-methanol in dichloromethane (1.0 mL) and triethylamine (0.100 mL, 0.717 mmol, excess) and add benzotriazol-1-yloxytris(dimethylamino)phosphonium hexfluorophosphate (BOP Reagent) (150 mg, 0.33 mmol, excess) at room temperature. Stir for 30 minutes, evaporate and load entire reaction directly onto pre-packed silica gel column and purify by flash column chromatography (EtOAc/Hexanes) to give 41 mg of (3-Hydroxymethyl-azetidin-1-yl)-[4-(3-phenyl-indole-1-sulfonyl)-phenyl]-methanone as a white solid (35%). LRMS: MH+ 447.2.

Workup

  1. customquench with 3.0 mL of 1.0M NaOH
  2. additiondilute with ether
  3. filtrationfilter through celite
  4. customevaporate
  5. additionTreat the resulting 3-hydroxymethyl-azetidine-1-carboxylic acid tert-butyl ester with 10 mL of trifluoroacetic acid for 20 minutes an evaporate
  6. customwithout further purification
  7. stirringStir for 30 minutes
  8. customevaporate
  9. customreaction directly onto pre-packed silica gel column
  10. custompurify by flash column chromatography (EtOAc/Hexanes)

Sources & evidence

ORD record
ord-69b27a67a28349cda5c63e723884e0a8
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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