Methanol → 14-Tert-butoxycarbonylamino-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]-nonadec-7-ene-4-carboxylic acid

HRID 346927Notes

Reaction equation

HRID 346927 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][CH:15]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:14](=[O:33])[N:13]1[CH:9]([CH2:10][CH:11]([O:34][C:35]3[C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[CH:38]=[CH:37][N:36]=3)[CH2:12]1)[C:8](=[O:45])[NH:7]2)=[O:5])C.C1COCC1.CO.O.[OH-].[Li+]>O>[C:29]([O:28][C:26]([NH:25][CH:15]1[C:14](=[O:33])[N:13]2[CH:9]([CH2:10][CH:11]([O:34][C:35]3[C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[CH:38]=[CH:37][N:36]=3)[CH2:12]2)[C:8](=[O:45])[NH:7][C:6]2([C:4]([OH:5])=[O:3])[CH:23]([CH2:24]2)[CH:22]=[CH:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)=[O:27])([CH3:32])([CH3:30])[CH3:31]

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 69489962HCID 69489962, compound

Product 1

HCID 7242743414-Tert-butoxycarbonylamino-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]-nonadec-7-ene-4-carboxylic acidYield 90.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

14-tert-butoxycarbonylamino-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]-nonadec-7-ene-4-carboxylic acid ethyl ester (1.10 g, 1.77 mmol) was dissolved in the mixed solvent system; THF (18 mL), methanol (8 mL), and water (2 mL). Powdered lithium hydroxide hydrate (744 mg, 17.7 mmol) was added. The light yellow slurry was stirred at rt under N2 for 24 h, and then concentrated in vacuo. The residue was partitioned between ether and water. The ether phase was discarded, and the aqueous phase was treated with 4N HCl until the pH was 4. This acidic solution was extracted with ether four times. The combined ether extracts were dried (MgSO4) and concentrated in vacuo to give 0.95 g (90%) of 14-tert-butoxycarbonylamino-18-(isoquinolin-1-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]-nonadec-7-ene-4-carboxylic acid as a white solid: 1H NMR (300 MHz, CD3Cl3) δ 1.30 (s, 9H), 1.34–1.46 (m, 4H), 1.52–1.68 (m, 2H), 1.84 (m, 2H), 2.08–2.58 (m, 6H), 2.78–2.87 (m, 1H), 4.07 (m, 1H), 4.32 (d, J=11.3 Hz, 1H), 4.41 (m, 1H), 4.79 (t, J=7.3 Hz, 1H), 5.14 (t, J=9.5 Hz, 1H), 5.23 (d, J=7.3 Hz, 1H), 5.60 (q, J=8.8 Hz, 1H), 5.86 (s, 1H), 7.08 (s, 1H), 7.22 (d, J=6.2 Hz, 1H), 7.48 (t, J=7.7 Hz, 1H), 7.64 (t, J=8.0 Hz, 1H), 7.72 (d, J=8.1 Hz, 1H), 7.94 (d, J=5.9 Hz, 1H), 8.17 (s, J=8.4 Hz, 1H). LC-MS (Method A, retention time: 3.32 min), MS m/z 593 (M++1)

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was partitioned between ether and water
  3. additionthe aqueous phase was treated with 4N HCl until the pH was 4
  4. extractionThis acidic solution was extracted with ether four times
  5. dry with materialThe combined ether extracts were dried (MgSO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5042c14db3464719ab90b85ea78a513d
Source dataset
uspto-grants-2007_02
Patent number
US07173004B2

Reaction notes

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