Diethyl Ether → HCID 68789384, compound

HRID 2069170Notes

Reaction equation

HRID 2069170 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([O:28][C:29]([N:31]3[CH2:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][C:37]=4[F:40])[CH2:32]3)=[O:30])[CH2:27][C@H:21]2[C:20](=[O:41])[NH:19][C@:18]2([C:43]([O:45]CC)=[O:44])[CH2:42][C@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][O:11][CH2:10]1)=[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[C:23](=[O:24])[N:22]2[CH2:25][C@H:26]([O:28][C:29]([N:31]3[CH2:39][C:38]4[C:33](=[CH:34][CH:35]=[CH:36][C:37]=4[F:40])[CH2:32]3)=[O:30])[CH2:27][C@H:21]2[C:20](=[O:41])[NH:19][C@:18]2([C:43]([OH:45])=[O:44])[CH2:42][C@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 68787215HCID 68787215, compound

Product 1

HCID 68789384HCID 68789384, compoundYield 82.5%

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-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa(i) pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecine-14a-carboxylate (0.16 g, 0.25 mmol) in THF (2 mL) was added 0.1 N NaOH solution (6.22 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-2,3,5,6,7,9,10,11,13a,14,14a,15,16,16a-tetradecahydro-1H-cyclopropa(i) pyrrolo[1,2-e][1,5,8]oxadiazacyclopentadecine-14a-carboxylic acid as white solid (0.13 g, 80%). MS: Calcd.: 630. Found: [M+H]+ 631. 1H NMR (400 MHz, d6-DMSO) M2.33 (s, 1H), 8.05 (d, J=19.6 Hz, 1H), 7.32 (m, 1H), 7.05-7.17 (m, 2H), 6.91 (m, 1H), 5.49 (m, 1H), 5.30 (m, 1H), 5.25 (s, 1H), 4.63 (s, 4H), 4.42 (m, 1H), 4.34 (m, 1H), 4.07 (m, 1H), 3.77 (m, 1H), 3.60 (m, 1H), 3.44 (m, 2H), 2.13-2.30 (m, 4H), 1.46-1.55 (m, 3H), 1.38 (m, 1H), 1.26 (m, 1H), 1.13-1.14 (m, 10H).

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-989ad5ee4f164011bb2865f06cbdb32f
Source dataset
uspto-grants-2012_10
Patent number
US08299021B2

Reaction notes

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