Triethylamine → HCID 67145028, compound

HRID 1695320Notes

Reaction equation

HRID 1695320 reaction equation
[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1[C:16]([O:17][CH3:18])=[CH:15][C:11]([C:12]([OH:14])=O)=[C:10]([N+:19]([O-:21])=[O:20])[CH:9]=1.C(Cl)(=O)C(Cl)=O.[CH3:28][O:29][C:30](=[O:37])[C@@H:31]1[CH2:35][C:34](=[CH2:36])[CH2:33][NH:32]1.CCN(CC)CC>CN(C=O)C.C1COCC1.O>[CH3:28][O:29][C:30](=[O:37])[C@@H:31]1[CH2:35][C:34](=[CH2:36])[CH2:33][N:32]1[C:12](=[O:14])[C:11]1[CH:15]=[C:16]([O:17][CH3:18])[C:8]([O:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][Br:1])=[CH:9][C:10]=1[N+:19]([O-:21])=[O:20]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 11002937HCID 11002937, compoundHCID 450899474-Methylene-L-proline methyl ester

Product 1

HCID 67145028HCID 67145028, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A catalytic amount of DMF (2 drops) was added to a solution of 4-(5-bromopentyloxy)-5-methoxy-2-nitro-benzoic acid 17 (270 mg, 0.74 mmol) and oxalyl chloride (80 μL, 0.89 mmol) in anhydrous THF (7.5 mL) and the resulting mixture was stirred at rt for an overnight. Excess THF and oxalyl chloride were removed with rotavapor. The acetyl chloride was resuspended in fresh THF (6 mL) and was added dropwise to a solution of 4-methylene-L-proline methyl ester 5 (228 mg, 0.89 mmol), Et3N (0.32 mL, 2.31 mmol), and H2O (0.15 mL) in THF (1.5 mL) at 0° C. under argon atmosphere. The reaction mixture was allowed to warm to rt and stirring was continued for 4 h. After removal of THF, the residue was partitioned between H2O and EtOAc (20/20 mL). The aqueous layer was further extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (20 mL), dried (MgSO4) and concentrated. Purification of the residue by flash chromatography (silica gel, 6:4 hexanes/EtOAc) yielded 1-[4-(5-bromopentyloxy)-5-methoxy-2-nitro-benzoyl]-4-methylene-L-proline methyl ester 18 as light yellow oil (rotamers): 1HNMR (300 MHz, CDCl3, rotamers) δ 1.62-1.68 (m, 2H), 1.86-1.98 (m, 4H), 2.64-2.75 (m, 1H), 2.99-3.08 (m, 1H), 3.43 (t, J=5.1 Hz, 2H), 3.59-3.96 (m, 7H), 4.05-4.21 (m, 3H), 4.57-4.61 and 4.90-5.12 (m, 3H), 6.80 and 6.83 (2 s, 1H), 7.64 and 7.67 (2 s, 1H); EIMS m/z 507 and 509 ([M]++Na).

Workup

  1. customExcess THF and oxalyl chloride were removed with rotavapor
  2. temperatureto warm to rt
  3. stirringstirring
  4. waitwas continued for 4 h
  5. customAfter removal of THF
  6. customthe residue was partitioned between H2O and EtOAc (20/20 mL)
  7. extractionThe aqueous layer was further extracted with EtOAc (3×10 mL)
  8. washThe combined organic layers were washed with brine (20 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customPurification of the residue by flash chromatography (silica gel, 6:4 hexanes/EtOAc)

Sources & evidence

ORD record
ord-72a635a0d0d74d7db5c0d4c74bb441ac
Source dataset
uspto-grants-2012_04
Patent number
US08163736B2

Reaction notes

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