Phthalimide → rac-Benzyl[1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4,4,4-trifluorobutan-2-yl]carbamate

HRID 1486257Notes

Reaction equation

HRID 1486257 reaction equation
[F:1][C:2]([F:19])([F:18])[CH2:3][CH:4]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:5]O.[C:20]1(=[O:30])[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22](=[O:29])[NH:21]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(/C(OC(C)(C)C)=O)=N\C(OC(C)(C)C)=O>C1COCC1.O.C(#N)C>[O:30]=[C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22](=[O:29])[N:21]1[CH2:5][CH:4]([NH:7][C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:3][C:2]([F:19])([F:18])[F:1]

Participants

7

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 90136009benzyl N-(4,4,4-trifluoro-1-hydroxybutan-2-yl)carbamate

Product 1

HCID 90135991rac-Benzyl[1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4,4,4-trifluorobutan-2-yl]carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

Under argon, 1.58 g of rac-benzyl (4,4,4-trifluoro-1-hydroxybutan-2-yl)carbamate (Example 43A, 5.70 mmol, 1 equivalent), 0.84 g of 1H-isoindole-1,3(2H)-dione (phthalimide, 5.70 mmol, 1 equivalent) and 2.24 g of triphenylphosphine (8.54 mmol, 1.5 equivalents) were dissolved in 28 ml of THF, and 1.84 g of di-tert-butyl (E)-diazene-1,2-dicarboxylate (DIAD, 8.54 mmol, 1.5 equivalents) were added at RT. The mixture was stirred at RT for 30 min and then a water/acetonitrile mixture was added. Purification by means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.1% TFA) gave 1.92 g (79% of theory) of the title compound.

Workup

  1. customPurification
  2. additionby means of preparative HPLC (RP18 column, eluent:acetonitrile/water gradient with addition of 0.1% TFA)

Sources & evidence

ORD record
ord-854e876f5a7842a39ff7b284b37e6368
Source dataset
uspto-grants-2016_08
Patent number
US09422285B2

Reaction notes

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