Pyridine → (5R,7R)-7-(4-bromophenyl)-3-oxa-1-azaspiro[4.4]nonan-2-one

HRID 2199466Notes

Reaction equation

HRID 2199466 reaction equation
[NH2:1][C@:2]1([CH2:14][OH:15])[CH2:6][CH2:5][C@@H:4]([C:7]2[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=2)[CH2:3]1.N1C=CC=CC=1.[C:22](N1C=CN=C1)(N1C=CN=C1)=[O:23]>C1COCC1.CCOC(C)=O>[Br:13][C:10]1[CH:11]=[CH:12][C:7]([C@@H:4]2[CH2:5][CH2:6][C@@:2]3([NH:1][C:22](=[O:23])[O:15][CH2:14]3)[CH2:3]2)=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 682631,1'-CarbonyldiimidazoleHCID 68263296((1R,3R)-1-amino-3-(4-bromophenyl)cyclopentyl)methanol

Product 1

HCID 86730035(5R,7R)-7-(4-bromophenyl)-3-oxa-1-azaspiro[4.4]nonan-2-oneYield 71.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

((1R,3R)-1-Amino-3-(4-bromophenyl)cyclopentyl)methanol (I-4A, 3.19 g, 11.81 mmol) was dissolved in THF (59.0 ml). Pyridine (0.955 ml, 11.81 mmol) and 1,1′-carbonyldiimidazole (5.74 g, 35.4 mmol) were added portionwise. The reaction mixture was stirred for 4 h and was followed by LCMS. After completion, the mixture was diluted with EtOAc and washed with 1M HCl. The aqueous layer was back extracted twice with EtOAc. The organic layers were combined, washed with saturated NaCl, dried over MgSO4, filtered and concentrated to afford (5R,7R)-7-(4-bromophenyl)-3-oxa-1-azaspiro[4.4]nonan-2-one (2.5 g, 8.44 mmol) after flash chromatography (24 g silica gel column; eluent: hexane 2 CV followed by a gradient to 100% EtOAc over 15 CV). HPLC ret time=0.91 min; LC/MS M+1=298. 1H NMR (400 MHz, CDCl3) δ 7.46 (d, J=8.5 Hz, 2H), 7.09 (d, J=8.5 Hz, 2H), 5.72-5.81 (m, 1H), 4.35 (dd, J=13 Hz, 8 Hz, 2H), 3.19-3.24 (m, 1H), 2.38-2.44 (m, 1H), 2.15-2.26 (m, 1H), 2.11-2.14 (m, 1H), 1.99-2.05 (m, 1H), 1.79-1.85 (m, 1H), 1.65-1.72 (m, 1H).

Workup

  1. washwashed with 1M HCl
  2. extractionThe aqueous layer was back extracted twice with EtOAc
  3. washwashed with saturated NaCl
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-6983522a5efb4efea9af6d12d82e7c56
Source dataset
uspto-grants-2016_06
Patent number
US09359286B2

Reaction notes

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