Phthalimide → HCID 57691455, compound

HRID 1867640Notes

Reaction equation

HRID 1867640 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH2:6][O:7][CH2:8][C:9]1([CH2:18][CH2:19]O)[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][O:10]1.[C:30]1(=[O:40])[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32](=[O:39])[NH:31]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[F:26][C:24]([F:25])([F:27])[C:22]1[CH:21]=[C:5]([CH:4]=[C:3]([C:2]([F:29])([F:28])[F:1])[CH:23]=1)[CH2:6][O:7][CH2:8][C:9]1([CH2:18][CH2:19][N:31]2[C:32](=[O:39])[C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:30]2=[O:40])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][O:10]1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 57691447HCID 57691447, compound

Product 1

HCID 57691455HCID 57691455, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(1-((3,5-bis(trifluoromethyl)benzyloxy)methyl)-1,3-dihydroisobenzofuran-1-yl)ethanol (200 mg, 0.48 mmol), isoindoline-1,3-dione (105 mg, 0.71 mmol), and triphenylphosphine (187 mg, 0.71 mmol) in tetrahydrofuran (5 mL) at 0° C. was added diethyl azodicarboxylate (0.112 mL, 0.71 mmol). The ice bath was removed and stirring continued for 1 h. Clean, complete conversion to product was observed. The reaction was quenched by addition of saturated ammonium chloride, and extracted with ethyl acetate (2×). The organics were washed with water, then saturated sodium bicarbonate, then brine, dried over magnesium sulfate, and concentrated. Column chromatography (8% EtOAc/Hex-->12% EtOAc/Hex) gave 255 mg (98%) as a colorless oil. 1H-NMR (CDCl3, 300 MHz) δ 7.73 (s, 1H), 7.67 (m, 2H), 7.63 (s, 2H), 7.61 (m, 2H), 7.00-7.15 (m, 4H), 5.16 (qAB, JAB=12.2 Hz, 2H), 4.60 (s, 2H), 3.77 (m, 1H), 3.68 (m, 1H), 3.63 (s, 2H), 2.47 (m, 1H), 2.30 (ddd, J=14.4, 7.3, 4.9 Hz, 1H); 13C-NMR (CDCl3, 126 MHz) δ 168.1, 141.2, 140.6, 140.0, 133.7, 132.2, 131.7 (q, J=33.6 Hz), 128.0, 127.4, 127.2, 123.4 (q, J=273 Hz), 122.9, 121.5, 121.4, 121.2, 88.9, 76.8, 73.0, 72.0, 33.6, 33.5. Mass spec.: 550.20 (MH)+.

Workup

  1. customThe ice bath was removed
  2. customThe reaction was quenched by addition of saturated ammonium chloride
  3. extractionextracted with ethyl acetate (2×)
  4. washThe organics were washed with water
  5. dry with materialsaturated sodium bicarbonate, then brine, dried over magnesium sulfate
  6. concentrationconcentrated
  7. customColumn chromatography (8% EtOAc/Hex-->12% EtOAc/Hex) gave 255 mg (98%) as a colorless oil

Sources & evidence

ORD record
ord-de8731ec983c41cca0b4b0704832f387
Source dataset
uspto-grants-2009_12
Patent number
US07632861B2

Reaction notes

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