Phthalimide → cis-tert-Butyl 2-(1,3-dioxoisoindolin-2-yl)cyclohexylcarbamate

HRID 711559Notes

Reaction equation

HRID 711559 reaction equation
O[C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:35]1(=[O:45])[NH:39][C:38](=[O:40])[C:37]2=[CH:41][CH:42]=[CH:43][CH:44]=[C:36]12.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1.C1(C)C=CC=CC=1>[O:40]=[C:38]1[C:37]2[C:36](=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:35](=[O:45])[N:39]1[C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 6809PhthalimideHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 10921888(1R,2R)-trans-N-Boc-2-Aminocyclohexanol

Product 1

HCID 67238263cis-tert-Butyl 2-(1,3-dioxoisoindolin-2-yl)cyclohexylcarbamateYield 244%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred slurry of trans-tert-butyl 2-hydroxycyclohexylcarbamate (1.00 g, 4.64 mmol), PPh3 (1.34 g, 5.10 mmol) and phthalimide (1.50 g, 10.20 mmol) in a 2:1 mixture of toluene and THF (15 mL) was added diisopropyl azodicarboxylate (1.0 mL, 5.10 mmol) dropwise over a period of 1 h. Once the addition was complete, the mixture was stirred at about 0° C. for 7 h and was then warmed slowly to 7° C. over a period of 14 h. The mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound as a yellow oil (3.90 g). The crude product was used in the next step without further purification.

Workup

  1. additionOnce the addition
  2. temperaturewas then warmed slowly to 7° C. over a period of 14 h
  3. filtrationThe mixture was filtered
  4. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-a2f5eb6ee65647d5b5e7da9dc096bcb8
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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