Diethyl Ether → (2R,6S,13aS,14aR,16aS, Z)-6-(tert-butoxycarbonylamino)-2-(4-fluoroisoindoline-2-carbonyloxy)-9-(2-nitrophenylsulfonyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa(n)pyrrolo[2,1-c][1,4,9]triazacyclopentadecine-14a-carboxylic acid

HRID 1171966Notes

Reaction equation

HRID 1171966 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:23][CH2:22][N:21]([S:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[N+:33]([O-:35])=[O:34])(=[O:26])=[O:25])[CH2:20][CH2:19][CH:18]=[CH:17][C@@H:16]2[CH2:36][C@@:15]2([C:37]([O:39]CC)=[O:38])[NH:14][C:13](=[O:42])[C@@H:12]2[CH2:43][C@@H:44]([O:46][C:47]([N:49]3[CH2:57][C:56]4[C:51](=[CH:52][CH:53]=[CH:54][C:55]=4[F:58])[CH2:50]3)=[O:48])[CH2:45][N:11]2[C:10]1=[O:59])=[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][N:21]([S:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[N+:33]([O-:35])=[O:34])(=[O:26])=[O:25])[CH2:20][CH2:19][CH:18]=[CH:17][C@@H:16]2[CH2:36][C@@:15]2([C:37]([OH:39])=[O:38])[NH:14][C:13](=[O:42])[C@@H:12]2[CH2:43][C@@H:44]([O:46][C:47]([N:49]3[CH2:57][C:56]4[C:51](=[CH:52][CH:53]=[CH:54][C:55]=4[F:58])[CH2:50]3)=[O:48])[CH2:45][N:11]2[C:10]1=[O:59])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 68791570(2R, 6S,13aS,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-2-(4-fluoroisoindoline-2-carbonyloxy)-9-(2-nitrophenylsulfonyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa(n)pyrrolo[2,1-c][1,4,9]triazacyclopentadecine-14a-carboxylate

Product 1

HCID 68792524(2R,6S,13aS,14aR,16aS, Z)-6-(tert-butoxycarbonylamino)-2-(4-fluoroisoindoline-2-carbonyloxy)-9-(2-nitrophenylsulfonyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa(n)pyrrolo[2,1-c][1,4,9]triazacyclopentadecine-14a-carboxylic acidYield 99.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

(2R,6S,13aS,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-2-(4-fluoroisoindoline-2-carbonyloxy)-9-(2-nitrophenylsulfonyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa(n)pyrrolo[2,1-c][1,4,9]triazacyclopentadecine-14a-carboxylate (1.45 g, 1.72 mmol) in THF (22 mL) was added 0.4 N NaOH solution (10.8 ml, 4.30 mmol) in water. The reaction was stirred at rt for 6 days. 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 (2×30 mL). the combined organics were 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)-9-(2-nitrophenylsulfonyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa(n)pyrrolo[2,1-c][1,4,9]triazacyclopentadecine-14a-carboxylic acid as white solid (1.40 g, 99%). MS: Calcd.: 814; Found: [M+H]+ 815. 1H NMR (400 MHz, d6-DMSO) δ11.24 (s, 1H), 8.84 (s, 1H), 8.01 (m, 2H), 7.86 (m, 2H), 7.36 (m, 1H), 7.10-7.26 (m, 3H), 5.49 (m, 1H), 5.39 (m, 1H), 5.27 (m, 1H), 4.67 & 4.66 (s, 4H), 4.40 (m, 1H), 4.27 (m, 1H), 3.97 (m, 1H), 3.66 (m, 1H), 3.31-3.53 (m, 2H), 3.23 (m, 1H), 2.96 (m, 1H), 2.55 (m, 1H), 2.25 (m, 2H), 1.99 (m, 2H), 1.91 (m, 2H), 0.96-1.69 (m, 11H).

Workup

  1. customThe aqueous layer was separated
  2. extractionThe aqueous layer was extracted with EA (2×30 mL)
  3. washthe combined organics were washed with brine
  4. dry with materialdried over sodium sulfate
  5. customAfter removal of solvent, it

Sources & evidence

ORD record
ord-3f6566290da143c3a0e231ec76c5817d
Source dataset
uspto-grants-2010_11
Patent number
US07829665B2

Reaction notes

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