Phthalimide → [(S)-5-benzyloxy-1-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-3,3-dimethyl-pentyl]carbamic acid tert-butyl ester

HRID 2365481Notes

Reaction equation

HRID 2365481 reaction equation
CCOC(/N=N/C(OCC)=O)=O.[C:13]([O:17][C:18](=[O:37])[NH:19][C@H:20]([CH2:35]O)[CH2:21][C:22]([CH3:34])([CH3:33])[CH2:23][CH2:24][O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([CH3:16])([CH3:15])[CH3:14].[C:38]1(=[O:48])[NH:42][C:41](=[O:43])[C:40]2=[CH:44][CH:45]=[CH:46][CH:47]=[C:39]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:13]([O:17][C:18](=[O:37])[NH:19][C@H:20]([CH2:35][N:42]1[C:38](=[O:48])[C:39]2[C:40](=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:41]1=[O:43])[CH2:21][C:22]([CH3:34])([CH3:33])[CH2:23][CH2:24][O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([CH3:16])([CH3:15])[CH3:14]

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 22882578((S)-5-benzyloxy-1-hydroxymethyl-3,3-dimethyl-pentyl)-carbamic acid tert-butyl ester

Product 1

HCID 67120699[(S)-5-benzyloxy-1-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-3,3-dimethyl-pentyl]carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DEAD (4.49 ml, 28 mmol) is added to a stirred suspension of ((S)-5-benzyloxy-1-hydroxymethyl-3,-3-dimethyl-pentyl)-carbamic acid tert-butyl ester (prepared as described in EP 0702004 A2, Rueger et al., 10 g, 0.028 mmol), phthalimide (4.19 g, 0.028 mmol) and PS-triphenylphosphine (29.8 g, 56 mmol) in THF (500 ml), and the resulting reaction is stirred at room temperature for 3 days. The reaction is filtered to remove the PS-triphenylphosphine resin and the resin is washed with EtOAc (2×50 ml). The solvent is removed in vacuo and the residue is purified by flash chromatography (SiO2, EtOAc/iso-hexane) to afford [(S)-5-benzyloxy-1-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-3,3-dimethyl-pentyl]-carbamic acid tert-butyl ester as a white solid; [M+H]+ 481.

Workup

  1. customthe resulting reaction
  2. filtrationThe reaction is filtered
  3. customto remove the PS-triphenylphosphine resin
  4. washthe resin is washed with EtOAc (2×50 ml)
  5. customThe solvent is removed in vacuo
  6. customthe residue is purified by flash chromatography (SiO2, EtOAc/iso-hexane)

Sources & evidence

ORD record
ord-995b00fd2d484427b1c60ba9813c8f7d
Source dataset
uspto-grants-2014_04
Patent number
US08697687B2

Reaction notes

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