Phthalimide → 1,1-dimethylethyl {(1S)-2-(4-bromophenyl)-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}carbamate

HRID 222882Notes

Reaction equation

HRID 222882 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:10]O)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:39]1(=[O:49])[NH:43][C:42](=[O:44])[C:41]2=[CH:45][CH:46]=[CH:47][CH:48]=[C:40]12.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:10][N:43]2[C:39](=[O:49])[C:40]3[C:41](=[CH:45][CH:46]=[CH:47][CH:48]=3)[C:42]2=[O:44])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 57594215Boc-L-4-Bromophenylalaninol

Product 1

HCID 575945641,1-dimethylethyl {(1S)-2-(4-bromophenyl)-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}carbamateYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,1-dimethylethyl [(1S)-2-(4-bromophenyl)-1-(hydroxymethyl)ethyl]carbamate (70.6 mmol), tripheylphosphine (84.7 mmol), and phthalimide (84.7 mmol) in anhydrous tetrahydrofuran (550 mL) at 0° C. was added dropwise diisopropyl azodicarboxylate (84.7 mmol) over 10 minutes. The reaction continued to stir allowing to warm to RT over 5 h. The reaction was then concentrated in vacuo and product was triturated out of solution using ethyl acetate (500 mL). The precipitate was filtered, washed with ethyl acetate (3×100 mL), and dried to afford the title product as a white solid (57%). ESMS [M+H]+: 460.4.

Workup

  1. concentrationThe reaction was then concentrated in vacuo and product
  2. customwas triturated out of solution
  3. filtrationThe precipitate was filtered
  4. washwashed with ethyl acetate (3×100 mL)
  5. customdried

Sources & evidence

ORD record
ord-1bb0cf47e41d4183ab6990d4b0c94bcb
Source dataset
uspto-grants-2012_06
Patent number
US08207340B2

Reaction notes

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