Phthalimide → tert-butyl {(1S)-2-cyclohexyl-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}carbamate

HRID 340002Notes

Reaction equation

HRID 340002 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][C@H:8]([CH2:16]O)[CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)([CH3:4])([CH3:3])[CH3:2].[C:19]1(=[O:29])[NH:23][C:22](=[O:24])[C:21]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:20]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.O1CCCC1>>[CH:10]1([CH2:9][C@H:8]([NH:7][C:6](=[O:18])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:16][N:23]2[C:19](=[O:29])[C:20]3[C:21](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:22]2=[O:24])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1

Participants

6

Reactant 5

HCID 6809PhthalimideHCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 11043405(S)-(-)-2-(tert-Butoxycarbonylamino)-3-cyclohexyl-1-propanol

Product 1

HCID 57544826tert-butyl {(1S)-2-cyclohexyl-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}carbamateYield 56%

Procedure

A mixture of tert-butyl[(1S)-2-cyclohexyl-1-(hydroxymethyl)ethyl]carbamate (3.3 g, 13 mmol), phthalimide (2.10 g, 14.3 mmol), triphenylphosphine (3.75 g, 14.3 mmol), diisopropyl azodicarboxylate (3.58 mL, 18.2 mmol) in tetrahydrofuran (30 mL, 400 mmol) was stirred at room temperature overnight. Direct purification by combi-flash chromatography afforded 2.8 g (56% yield) of the desired product. LC-MS found: 287.1 (M−Boc)+.

Workup

  1. customDirect purification by combi-flash chromatography

Sources & evidence

ORD record
ord-e9a59f37e767480391c914f5f721919e
Source dataset
uspto-grants-2014_11
Patent number
US08895571B2

Reaction notes

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