Water → (1S,4R,6S,14S,18R)-7-cis-14-tert-Butoxycarbonylamino-18-(tert-butyldimethylsilyloxy)-2,15-dioxo-3,12,16-triazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid

HRID 500414Notes

Reaction equation

HRID 500414 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:27](=[O:28])[N:26]2[C@@H:22]([CH2:23][C@@H:24]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH2:25]2)[C:21](=[O:37])[NH:20][C@@:19]2([C:38]([O:40]CC)=[O:39])[C@@H:17]([CH2:18]2)[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][NH:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.O.[OH-].[Li+]>C1COCC1.CO>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:27](=[O:28])[N:26]2[C@@H:22]([CH2:23][C@@H:24]([O:29][Si:30]([C:33]([CH3:35])([CH3:34])[CH3:36])([CH3:32])[CH3:31])[CH2:25]2)[C:21](=[O:37])[NH:20][C@@:19]2([C:38]([OH:40])=[O:39])[C@@H:17]([CH2:18]2)[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][NH:11][CH2:10]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 86612090(1S, 4R, 6S, 14S, 18R)-7-cis-14-tert-Butoxycarbonylamino-18-(tert-butyldimethylsilyloxy)-2,15-dioxo-3,12,16-triazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid, ethyl ester

Product 1

HCID 86612089(1S,4R,6S,14S,18R)-7-cis-14-tert-Butoxycarbonylamino-18-(tert-butyldimethylsilyloxy)-2,15-dioxo-3,12,16-triazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acidYield 61.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1S,4R,6S,14S,18R)-7-cis-14-tert-Butoxycarbonylamino-18-(tert-butyldimethylsilyloxy)-2,15-dioxo-3,12,16-triazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid, ethyl ester (0.84 g, 1.30 mmoL) in THF (30 mL), methanol (15 mL), and water (4 mL), was added powdered lithium hydroxide hydrate (0.31 g, 12.90 mmoL). The resultant light yellow slurry was stirred at rt under N2 overnight. The mixture was then concentrated in vacuo, and partitioned between hexane/ether (1:1) and water. The organic phase was discarded, and the aqueous phase was treated with 1 N HCl until pH 5. This acidic solution was extracted with EtOAc (3×). The combined EtOAc extracts were dried (MgSO4) and concentrated in vacuo to give 0.495 g (61%) of (1S,4R,6S,14S,18R)-7-cis-14-tert-Butoxycarbonylamino-18-(tert-butyldimethylsilyloxy)-2,15-dioxo-3,12,16-triazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid as an off-white solid: LC-MS (Phenomenex 10 μm C18HPLC column: 3.0×50 mm length. Gradient: 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B. Gradient time: 2 min. Hold time: 1 min. Flow rate: 5 mL/min. Detector Wavelength: 220 nM. Solvent A: 10% MeOH/90% H2O/0.1% TFA. Solvent B: 10% H2O/90% MeOH/0.1% TFA.) (Retention time: 2.36 min), MS m/z 621 (M++1).

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. custompartitioned between hexane/ether (1:1) and water
  3. additionthe aqueous phase was treated with 1 N HCl until pH 5
  4. extractionThis acidic solution was extracted with EtOAc (3×)
  5. dry with materialThe combined EtOAc extracts were dried (MgSO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-664b0c45fa0e4ffaa5e0ad9c8f879c0f
Source dataset
uspto-grants-2010_08
Patent number
US07772183B2

Reaction notes

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