Diethyl Ether → HCID 68789801, compound

HRID 1171952Notes

Reaction equation

HRID 1171952 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:23][CH2:22][CH2:21][O:20][CH2:19][CH:18]=[CH:17][C@@H:16]2[CH2:24][C@@:15]2([C:25]([O:27]CC)=[O:26])[NH:14][C:13](=[O:30])[C@@H:12]2[CH2:31][C@@H:32]([O:34][C:35]([N:37]3[CH2:45][C:44]4[C:39](=[CH:40][CH:41]=[CH:42][C:43]=4[F:46])[CH2:38]3)=[O:36])[CH2:33][N:11]2[C:10]1=[O:47])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].CCOCC>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:23][CH2:22][CH2:21][O:20][CH2:19][CH:18]=[CH:17][C@@H:16]2[CH2:24][C@@:15]2([C:25]([OH:27])=[O:26])[NH:14][C:13](=[O:30])[C@@H:12]2[CH2:31][C@@H:32]([O:34][C:35]([N:37]3[CH2:45][C:44]4[C:39](=[CH:40][CH:41]=[CH:42][C:43]=4[F:46])[CH2:38]3)=[O:36])[CH2:33][N:11]2[C:10]1=[O:47])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 68789716HCID 68789716, compound

Product 1

HCID 68789801HCID 68789801, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

(2R,6S,13aS,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-2-(4-fluoroisoindoline-2-carbonyloxy)-5,16-dioxo-2,3,5,6,7,8,9,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa(e)pyrrolo[2,1-i][1,7,10]oxadiazacyclopentadecine-14a-carboxylate (0.18 g, 0.27 mmol) in THF (2 mL) was added 0.1 N NaOH solution (6.64 ml, 0.62 mmol) in H2O. The reaction was stirred at rt for 26 hr. Water (5 mL) and ether (15 mL) was added. The aqueous layer was separated and acidified by saturated potassium hydrogen sulfate solution to pH=2˜3. The aqueous layer was extracted with EA (2×15 mL), washed with brine and dried over sodium sulfate. After removal of solvent, it gave (2R,6S,13aS,14aR,16aS,Z)-6-(tert-butoxycarbonylamino)-2-(4-fluoroisoindoline-2-carbonyloxy)-5,16-dioxo-2,3,5,6,7,8,9,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa(e)pyrrolo[2,1-i][1,7,10]oxadiazacyclopentadecine-14a-carboxylic acid as white solid (0.15 g, 92%). MS: Calcd.: 630; Found: [M+H]+ 631. 1H NMR (400 MHz, d6-DMSO) δ12.29 (s, 1H), 8.59 (d, J=13.2 Hz, 1H), 7.36 (m, 1H), 7.10-7.20 (m, 3H), 5.59 (m, 1H), 5.50 (m, 1H), 5.30 (s, 1H), 4.66 (s, 4H), 4.51 (m, 1H), 4.41 (m, 1H), 4.23 (m, 1H), 3.94 (m, 1H), 3.74 (m, 1H), 3.50 (m, 1H), 3.37 (m, 2H), 2.35 (m, 1H), 1.78 (m, 2H), 1.51 (m, 2H), 1.37 (m, 2H), 1.24 (m, 2H), 1.08 & 1.09 (s, 9H).

Workup

  1. customThe aqueous layer was separated
  2. extractionThe aqueous layer was extracted with EA (2×15 mL)
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. customAfter removal of solvent, it

Sources & evidence

ORD record
ord-081ff3f6d22445be9c491f3983b2af89
Source dataset
uspto-grants-2010_11
Patent number
US07829665B2

Reaction notes

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