Tetrahydrofuran → HCID 58909281, compound

HRID 1296089Notes

Reaction equation

HRID 1296089 reaction equation
[CH2:1]([Zn])[C:2]([CH3:5])([CH3:4])[CH3:3].C1COCC1.I[C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[O:19][CH2:18][CH2:17][C@@H:16]2[NH:23]C(=O)OC(C)(C)C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]([C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[O:19][CH2:18][CH2:17][C@@H:16]2[NH2:23])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 58909246HCID 58909246, compoundHCID 178445876HCID 178445876, compound

Product 1

HCID 58909281HCID 58909281, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

To a suspension of the 0.3 M neopentyl zinc reagent in THF (60 ml, 15 mmol) was added the tert-butyl (4S)-6-iodo-3,4-dihydro-2H-chromen-4-ylcarbamate (1.8 g, 5.0 mmol) and Pd(dppf)Cl2 (0.2 g, 0.25 mmol) as solids in one portion. The mixture was stirred at r.t. under nitrogen for 48 hours (progress monitored by LC/MS and HPLC). The mixture was quenched with aqueous NH4Cl (20 ml) and extracted with EtOAc (3×50 ml). The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude residue was dissolved in MeOH(25 ml) and treated with DOWEX® 50WX2-400 ion exchange resin. The mixture was heated to 50° C. for six hours and then the resing was collected by filtration. The resin was washed successively with MeOH and CH2Cl2 these washings were discarded. The resin was then treated with 7 N NH3/MeOH to elute the free amine from the resin. The elutions were concentrated in vacuo to yield a light brown oil (0.63 g, 57%) of (4S)-6-neopentyl-3,4-dihydro-2H-chromen-4-ylamine. This material was consistent with previous preparations and was used as obtained for the subsequent opening of the di-fluoroPhe epoxide. S)-6-neopentyl-3,4-dihydro-2H-chromen-4-ylamine was previously characterized as the mono.HCl salt. 1H NMR (300 MHz, DMSO-d6) δ); 7.25 (s, 1H), 7.02 (m, 1H,), 6.76 (m, 1H), 4.47 (bs, 1H), 4.21 (m, 2H), 2.38 (s, 2H), 2.24 (m, 1H), 2.10 (m, 1H), 0.87 (s, 9H). HRMS (ESI+) calculated for C14H21N1O1 220.1701; found m/z 220.1698 (M+H)+. Anal. Calcd for C14H21NO.HCl: C, 65.74; H, 8.67; N, 5.48. Found: C, 65.62; H, 8.53; N, 5.42. [α]23D=15.6, c=1.17 in CH3OH.

Workup

  1. customThe mixture was quenched with aqueous NH4Cl (20 ml)
  2. extractionextracted with EtOAc (3×50 ml)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude residue was dissolved in MeOH(25 ml)
  6. additiontreated with DOWEX® 50WX2-400 ion exchange resin
  7. temperatureThe mixture was heated to 50° C. for six hours
  8. filtrationthe resing was collected by filtration
  9. washThe resin was washed successively with MeOH and CH2Cl2 these washings
  10. additionThe resin was then treated with 7 N NH3/MeOH
  11. washto elute the free amine from the resin
  12. concentrationThe elutions were concentrated in vacuo

Sources & evidence

ORD record
ord-7fe223a902b348ac9452e8805d265262
Source dataset
uspto-grants-2007_07
Patent number
US07244725B2

Reaction notes

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