Lithium Hydroxide → 18-Ethoxymethoxy-14-(4-methoxy-benzyl)-2,15-dioxo-3,14,16-triaza-tricyclo[14.3.0.0*4,6*]nonadec-7-ene-4-carboxylic acid

HRID 390130Notes

Reaction equation

HRID 390130 reaction equation
C([O:3][C:4]([C:6]12[CH2:24][CH:23]1[CH:22]=[CH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][N:15]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[C:14](=[O:34])[N:13]1[CH:9]([CH2:10][CH:11]([O:35][CH2:36][O:37][CH2:38][CH3:39])[CH2:12]1)[C:8](=[O:40])[NH:7]2)=[O:5])C.C1COCC1.CO.[Li+].[OH-]>ClCCl.CO>[CH2:38]([O:37][CH2:36][O:35][CH:11]1[CH2:10][CH:9]2[N:13]([C:14](=[O:34])[N:15]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH:21]=[CH:22][CH:23]3[C:6]([C:4]([OH:5])=[O:3])([NH:7][C:8]2=[O:40])[CH2:24]3)[CH2:12]1)[CH3:39]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 21899815MeOH tetrahydrofuranHCID 6687066618-Ethoxymethoxy-14-(4-methoxy-benzyl)-2,15-dioxo-3,14,16-triaza-tricyclo-[14.3.0.0*4,6*]nonadec-7-ene-4-carboxylic acid ethyl ester

Product 1

HCID 6687062318-Ethoxymethoxy-14-(4-methoxy-benzyl)-2,15-dioxo-3,14,16-triaza-tricyclo[14.3.0.0*4,6*]nonadec-7-ene-4-carboxylic acidYield 101.9%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

A solution of the ester 21g (0.775 g, 1.39 mmol) in 1:1:1 THF-Methanol-aq. 1M LiOH (36 ml) was stirred at rt for 3.5 h after which TLC (95:5 and 9:1 dichloromethane-methanol) and LC-MS indicated complete conversion into the carboxylic acid. The reaction mixture was then concentrated into approximately ⅓ of the volume, then diluted with water (10 ml) and acidified to approx. pH 4 using aq. 10% citric acid (60 ml) upon which a precipitate formed. The mixture was washed with ethyl acetate (3×25 ml) and the combined organic layers were washed with brine (2×50 ml), then dried (Na2SO4), filtered and concentrated. The residue was concentrated from toluene (3×10 ml) which gave the crude title compound as an off-white foam (0.75 g, quantitative). LR-MS: Calcd for C28H40N3O7: 530. Found: 530 [M−H].

Workup

  1. concentrationThe reaction mixture was then concentrated into approximately ⅓ of the volume
  2. additiondiluted with water (10 ml)
  3. customformed
  4. washThe mixture was washed with ethyl acetate (3×25 ml)
  5. washthe combined organic layers were washed with brine (2×50 ml)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. concentrationThe residue was concentrated from toluene (3×10 ml) which

Sources & evidence

ORD record
ord-bccddc0dd6a748c0958a92e49b47f787
Source dataset
uspto-grants-2013_02
Patent number
US08383584B2

Reaction notes

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