Hydrochloric Acid → (3aS,5S,6aR)-5-(1,3-dioxoisoindolin-2-yl)-N-(2-hydroxy-5-(trifluoromethyl)benzyl)hexahydro-2H-cyclopenta[b]furan-3a-carboxamide

HRID 1747153Notes

Reaction equation

HRID 1747153 reaction equation
Cl.Cl.[NH2:3][C@@H:4]1[CH2:11][C@H:7]2[O:8][CH2:9][CH2:10][C@@:6]2([C:12]([NH:14][CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=2[OH:26])=[O:13])[CH2:5]1.[C:27]1(=O)[O:32][C:30](=[O:31])[C:29]2=[CH:33][CH:34]=[CH:35][CH:36]=[C:28]12.CCN(C(C)C)C(C)C.C(C1NC=CN=1)(C1NC=CN=1)=O.Cl>C(Cl)(Cl)Cl>[O:31]=[C:30]1[C:29]2[C:28](=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:27](=[O:32])[N:3]1[C@@H:4]1[CH2:11][C@H:7]2[O:8][CH2:9][CH2:10][C@@:6]2([C:12]([NH:14][CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[CH:18][C:17]=2[OH:26])=[O:13])[CH2:5]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6811Phthalic AnhydrideHCID 81531DiisopropylethylamineHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 86708151(3aS,5S,6aR)-5-amino-N-(2-hydroxy-5-(trifluoromethyl)benzyl)hexahydro-2H-cyclopenta[b]furan-3a-carboxamide dihydrochloride

Product 1

HCID 86708154(3aS,5S,6aR)-5-(1,3-dioxoisoindolin-2-yl)-N-(2-hydroxy-5-(trifluoromethyl)benzyl)hexahydro-2H-cyclopenta[b]furan-3a-carboxamide

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A solution of the product of Step B (8.58 g, 18.74 mmol, 1 eq), phthalic anhydride (5.55 g, 37.5 mmol, 2 eq) and DIEA (11.3 mL, 55.6 mmol, 3.5 eq) in chloroform (150 mL) was heated to 70° C. for 2 hours. The solution was cooled to rt and carbonyl diimidazole (2.24 g 13.82 mmol, 3 eq) was added and the solution heated to 60° C. for 2 hours. The solution was cooled to rt, 1 N HCl was added, the aqueous extracted with DCM, the organics combined, dried over MgSO4 and concentrated. Purification by chromatography (200 g column) eluting with 30 to 60 to 80% EA/heptane afforded the product of Step C. Calculated for C24H21F3N2O5: 474.1 (M+1). found: 475.1.

Workup

  1. temperaturethe solution heated to 60° C. for 2 hours
  2. temperatureThe solution was cooled to rt
  3. extractionthe aqueous extracted with DCM
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customPurification by chromatography (200 g column)
  7. washeluting with 30 to 60 to 80% EA/heptane

Sources & evidence

ORD record
ord-d4641f26d4734c97a2cc4c9226705bcc
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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