Trichloroacetonitrile → HCID 131728731, compound

HRID 600150Notes

Reaction equation

HRID 600150 reaction equation
[C:1]([O:4][C@@H:5]1[C@H:19]([O:20][C:21]([O:23][CH2:24][C:25]2[C:37]3[CH2:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:29]=3[CH:28]=[CH:27][CH:26]=2)=[O:22])[C@@H:18]([O:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C@H:17]([CH3:46])[O:16][C@H:6]1[O:7]C1C=CC(OC)=CC=1)(=[O:3])[CH3:2].[N+]([O-])([O-])=O.[NH4+].[Ce].[H-].[Na+].[Cl:55][C:56]([Cl:60])([Cl:59])[C:57]#[N:58]>C1(C)C=CC=CC=1.C(#N)C.O.ClCCl>[Cl:55][C:56]([Cl:60])([Cl:59])[C:57](=[NH:58])[O:7][C@@H:6]1[O:16][C@@H:17]([CH3:46])[C@H:18]([O:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C@@H:19]([O:20][C:21]([O:23][CH2:24][C:25]2[C:37]3[CH2:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:29]=3[CH:28]=[CH:27][CH:26]=2)=[O:22])[C@H:5]1[O:4][C:1](=[O:3])[CH3:2]

Participants

9

Reactant 4

HCID 11011TrichloroacetonitrileHCID 24758Sodium hydrideHCID 57418452Ammonium cerium-nitrateHCID 86631772HCID 86631772, compound

Product 1

HCID 131728731HCID 131728731, compoundYield 94%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

4-Methoxyphenyl 2-O-acetyl-4-O-benzyl-α-L-rhamnopyranoside (12) (4.57 g, 11.36 mmol) was dissolved in 60 mL of pyridine. FmocCl (5.88 g, 22.73 mmol) was added in one portion and the mixture stirred for 2 h at room temperature. Pyridine was removed in vacuo and the residue adsorbed on silica gel. 6.21 g (88%) of pure 4-methoxyphenyl 2-O-acetyl-4-O-benzyl-3-O-fluorenylmethoxycarbonyl-α-L-rhamnopyranoside were obtained by column chromatography (5:1→4:1→3:1 hexane/EtOAc). 4-Methoxyphenyl 2-O-acetyl-4-O-benzyl-3-O-fluorenylmethoxycarbonyl-α-L-rhamnopyranoside (3.10 g, 4.96 mmol) was dissolved in a mixture of 55 mL of toluene, 80 mL of acetonitrile and 55 mL of water. Cerium ammonium nitrate (21.7 g, 39.7 mmol) was added and the mixture was vigorously stirred for 80 min at room temperature. After TLC showed complete removal of the MP group, the phases of the mixture were separated, the organic phase was washed 2 times with water, saturated aqueous NaHCO3, then again once with water, dried over Na2SO4 and was concentrated. The resulting crude product was adsorbed on silica gel and purified by column chromatography (3:1→2:1 hexane/EtOAc) to afford 1.95 g (76%) of 2-acetyl-4-benzyl-3-fluorenylmethoxycarbonyl-L-rhamnopyranoside as a slightly yellow solid. This compound (675 mg, 1.30 mmol) was dissolved in 6 mL of tricloroacetonitrile and 7 mL of dichloromethane. A catalytic amount of sodium hydride (10 mg) was added and the mixture stirred for 60 min. The solvent was removed in vacuo and the residue purified by flash column chromatography (2:1 hexane/EtOAc) to afford 810 mg (94%) of 13 (only traces of P product) as a slightly yellow oil: [α]D: −17.3 (c=0.51, CHCl3), IR (thin film, CHCl3): 3026, 1754, 1672, 1451, 1380, 1262, 1067 cm−1. 1H NMR (CDCl3, 300 MHz) δ 1.41 (d, J=6.0 Hz, 3H), 2.22 (s, 3H), 3.69 (t, J=9.3 Hz, 1H), 4.11 (m, 1H), 4.33 (m, 2H), 4.52 (m, 1H), 4.68 (d, J=11.1 Hz, 1H), 4.86 (d, J=11.1 Hz, 1H), 5.26 (dd, J=12.3 Hz, J=3.3 Hz, 1H), 5.61 (m, 1H), 6.23 (s, 1H), 7.28 (m, 7H), 7.39 (m, 2H), 7.60 (m, 2H), 7.77 (d, J=6.6 Hz, 2H), 8.71 (s, 1H). 13C NMR (CDCl3, 75 MHz) 18.1, 21.0, 46.7, 68.4, 70.3, 70.6, 75.5, 75.6, 77.8, 94.7, 120.0, 124.9, 125.1, 127.1, 127.7, 127.8, 127.9, 128.4, 137.4, 141.1, 141.2, 142.9, 143.4, 154.0, 160.0, 169.6. MALDI-HRMS: m/z [M+Na]+ calcd 684.0929, obsd 684.0939.

Workup

  1. customremoval of the MP group
  2. customthe phases of the mixture were separated
  3. washthe organic phase was washed 2 times with water, saturated aqueous NaHCO3
  4. dry with materialagain once with water, dried over Na2SO4
  5. concentrationwas concentrated
  6. custompurified by column chromatography (3:1→2:1 hexane/EtOAc)
  7. customto afford 1.95 g (76%) of 2-acetyl-4-benzyl-3-fluorenylmethoxycarbonyl-L-rhamnopyranoside as a slightly yellow solid
  8. stirringthe mixture stirred for 60 min
  9. customThe solvent was removed in vacuo
  10. customthe residue purified by flash column chromatography (2:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-e8c7e70b2d0145688d74260e4eb6cfae
Source dataset
uspto-grants-2011_03
Patent number
US07901687B2

Reaction notes

Loading…