Dichloromethane → Succinate

HRID 907485Notes

Reaction equation

HRID 907485 reaction equation
[CH3:1][C@H:2]([C:15]([OH:17])=[O:16])[C:3]1[CH:4]=[CH:5][C:6]2[CH:7]=[C:8]([O:13][CH3:14])[CH:9]=[CH:10][C:11]=2[CH:12]=1.[NH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([OH:26])=[O:25].[NH2:27][CH:28]([CH2:31][OH:32])[CH2:29][OH:30].[C:33]1(=[O:39])[O:38][C:36](=[O:37])[CH2:35][CH2:34]1.ClCCl>CN(C1C=CN=CC=1)C.C(Cl)CCl>[CH3:1][C@H:2]([C:15]([OH:17])=[O:16])[C:3]1[CH:4]=[CH:5][C:6]2[CH:7]=[C:8]([O:13][CH3:14])[CH:9]=[CH:10][C:11]=2[CH:12]=1.[NH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([OH:26])=[O:25].[NH2:27][CH:28]([CH2:31][OH:32])[CH2:29][OH:30].[CH2:35]([C:36]([O-:13])=[O:37])[CH2:34][C:33]([O-:38])=[O:39]

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 7922Succinic anhydrideHCID 131727751HCID 131727751, compound

Product 2

HCID 160419SuccinateYield 1,363.6%HCID 131727751HCID 131727751, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolvent

Procedure

The desired solid support 8a was prepared according to reported procedures (References for succinilation: Rajeev et al., Org. Lett., 2003, 5, 3005 and for conjugation to CPG: Kumar et al., Nucleosides Nucleotides, 1996, 15, 879). A mixture of compound 7a (1.00 g, 1.39 mmol), succinic anhydride (0.17 g, 1.69 mmol, purchased from Aldrich) and DMAP (0.21 g, 1.72 mmol) were suspended in 7 mL of anhydrous ethylene dichloride for 24 h. Reaction mixture was diluted to 50 mL by adding dichloromethane and washed with dilute aqueous citric acid solution (20 mL), dried over anhydrous Na2SO4 and evaporated to dryness. The residue obtained was further dried over P2O5 under vacuum to afford an almost pure but crude monosuccinate as a white solid (1.10 g, 96.5%). The product obtained was directly used for subsequent reaction without further purification. 1H NMR (400 MHz, [D6]DMSO, 25° C.): δ 7.94-7.91 (t, J(H,H)=5.19, 5.49 Hz, 1H, exchangeable with D2O), 7.83-7.81 (d, J(H,H)=7.94 Hz, 1H, exchangeable with D2O), 7.76-7.68 (m, 3H), 7.42-7.10 (m, 12H), 6.88-6.86 (d, 4H), 4.18-4.12 (m, 2H), 4.07-3.98 (m, 2H), 3.83 (s, 3H), 3.71-3.66 (m, 7H), 3.00-2.91 (m, 4H), 2.40 (s, 4H), 2.04-2.00 (t, J(H,H)=7.32 Hz, 2H), 1.44-1.22 (m, 7H), 1.19-1.15 (m, 2H).

Workup

  1. customReaction mixture
  2. additionwas diluted to 50 mL
  3. washwashed with dilute aqueous citric acid solution (20 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. customevaporated to dryness
  6. customThe residue obtained
  7. dry with materialwas further dried over P2O5 under vacuum

Sources & evidence

ORD record
ord-db440a1ccaaf4edab2be202d79c721d4
Source dataset
uspto-grants-2011_09
Patent number
US08013136B2

Reaction notes

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