Tert-butyl octahydropyrrolo(3,4-c)pyrrole-2-carboxylate → 2-(7-Boc-3,7-diazabicyclo[3.3.0]oct-3-yl)-xanthen-9-one

HRID 553053Notes

Reaction equation

HRID 553053 reaction equation
[C:1]([N:8]1[CH2:15][CH:14]2[CH:10]([CH2:11][NH:12][CH2:13]2)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].I[C:17]1[CH:30]=[CH:29][C:28]2[O:27][C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20](=[O:31])[C:19]=2[CH:18]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([N:8]1[CH2:9][CH:10]2[CH:14]([CH2:13][N:12]([C:23]3[CH:24]=[CH:25][C:26]4[O:27][C:28]5[C:19](=[CH:18][CH:17]=[CH:30][CH:29]=5)[C:20](=[O:31])[C:21]=4[CH:22]=3)[CH2:11]2)[CH2:15]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

7

Reactant 3

HCID 4142526Tert-butyl octahydropyrrolo(3,4-c)pyrrole-2-carboxylateHCID 139791862-Iodoxanthen-9-oneHCID 23676156Sodium t-butoxide

Product 1

HCID 671633442-(7-Boc-3,7-diazabicyclo[3.3.0]oct-3-yl)-xanthen-9-oneYield 61%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 3-Boc-3,7-diazabicyclo[3.3.0]octane (235 mg, 1.11 mmol; see WO 0181347), 2-iodoxanthen-9-one (362 mg, 1.12 mmol; see Example 52A), tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3; 22 mg, 0.024 mmol; Alfa), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 37 mg, 0.059 mmol; Strem) and sodium tert-butoxide (166 mg, 1.73 mmol; Acros) in toluene (5 mL) was flushed with nitrogen and warmed to 85° C. with vigorous stirring for 6 h. The reaction mixture was cooled to ambient temperature, filtered through diatomaceous earth with an EtOAc rinse, concentrated under reduced pressure, and purified by flash chromatography (35 g silica gel, 5-50% gradient of EtOAc in hexanes) to afford the title compound as a yellow foam (275 mg, 0.677 mmol; 61% yield): 1H NMR (300 MHz, CDCl3) δ ppm 8.35 (dd, J=8, 2 Hz, 1H), 7.69 (ddd, J=9, 7, 2 Hz, 1H), 7.47 (d, J=8 Hz, 1H), 7.43 (d, J=9 Hz, 1H), 7.30-7.38 (m, 2H), 7.05 (dd, J=9, 3 Hz, 1H), 3.57-3.73 (m, 4H), 3.24-3.45 (m, 4H), 2.97-3.12 (m, 2H), 1.46 (s, 9H); MS (DCI/NH3): m/z 407 (M+1)+.

Workup

  1. customwas flushed with nitrogen
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. filtrationfiltered through diatomaceous earth with an EtOAc
  4. washrinse
  5. concentrationconcentrated under reduced pressure
  6. custompurified by flash chromatography (35 g silica gel, 5-50% gradient of EtOAc in hexanes)

Sources & evidence

ORD record
ord-0110bb792d7249d7b1889262e6b2e0e0
Source dataset
uspto-grants-2011_05
Patent number
US07951791B2

Reaction notes

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