Dichloroacetic Acid → N6-Benzoyl-5'-O-(t-butyldimethylsilyl)-2',3'-dideoxy-2'-oxoadenosine

HRID 37396Notes

Reaction equation

HRID 37396 reaction equation
[C:1]([NH:9][C:10]1[C:11]2[N:12]=[CH:13][N:14]([C:30]=2[N:31]=[CH:32][N:33]=1)[C@@H:15]1[O:29][C@H:19]([CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH2:18][C@H:16]1[OH:17])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.CN(C)CCCN=C=NCC.ClC(Cl)C(O)=O>CS(C)=O.C1C=CC=CC=1.ClCCl>[C:1]([NH:9][C:10]1[C:11]2[N:12]=[CH:13][N:14]([C:30]=2[N:31]=[CH:32][N:33]=1)[C@@H:15]1[O:29][C@H:19]([CH2:20][O:21][Si:22]([C:25]([CH3:27])([CH3:28])[CH3:26])([CH3:24])[CH3:23])[CH2:18][C:16]1=[O:17])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 6597Dichloroacetic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11178870N6-benzoyl-5'-O-(t-butyldimethylsilyl)-3'-deoxyadenosine

Product 1

HCID 14192246N6-Benzoyl-5'-O-(t-butyldimethylsilyl)-2',3'-dideoxy-2'-oxoadenosineYield 79.4%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2.0 g (5.47 mmol) 5'-O-(t-butyldimethylsilyl)-3'-deoxyadenosine, the product of Example 13, in 11 mL of pyridine at room temperature was added 2.5 mL (21.9 mmol) of benzoyl chloride. After 2 h, 1 mL of methanol was added, the reaction mixture was diluted with ether, washed successively with water and 50% saturated aqueous sodium bicarbonated, and dried over magnesium sulfate. The organic phase was evaporated under reduced pressure and then coevaporated with several portions of n-heptane to afford 3.9 g of a foam. To a stirred solution of 3.8 g of this residue in 44 ml of dioxane were added 16.8 mL of 1N aqueous NaOH. After 2 hours 5.6 mL additional 1N aqueous NaOH were added, After a total of 2.5 hours, the reaction mixture was neutralized with acetic acid, diluted with EtOAc, washed successively with water and saturated aqueous NaCl, dried over magnesium sulfate, and then concentrated under reduced pressure. Chromatography of the residue on silica gel with a 100:0 to 95:5 EtOAc/MeOH gradient afforded 1.94 g (75%) of N6-benzoyl-5'-O-(t-butyldimethylsilyl)-3'-deoxyadenosine. To a stirred solution of 880 mg (1.87 mmol) of N6-benzoyl-5'-O-(t-butyldimethylsilyl)-3'-deoxyadenosine in 9 mL of DMSO and 9 mL of benzene at room temperature containing 1.80 g (9.37 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added 4 portions of 0.031 mL (0.37 mmol) of dichloroacetic acid at 15 minute intervals. Fifteen minutes after the final addition, the reaction mixture was diluted with dichloromethane and washed with water adjusted to pH 3 with 1N aqueous HCl. The aqueous phase was extracted several times with dichloromethane, the combined organic extracts dried over magnesium sulfate, and then concentrated under reduced pressure. Chromatography of the residue on silica gel with a 75:25 to 100:0 EtOAc/hexane gradient afforded 694 mg (79%) of the title compound: Colorless glass. Rf =0.40 (SG, EtOAc); [α]D23 -17.0° (c 1.25, CHCl3); IR (CDCl3) 3415, 2960, 2935, 2860, 1775, 1710, 1610, 1590, 1455, 1255, 1240, 1070 cm-1 ; 1H-NMR (300 MHz, CDCl3, TMS=0.00 ppm) δ0.05, 0.07 (2s, 6H, (CH3)2Si), 0.90 (s, 9H, (CH3)3CSi), 2.86 (dd, 1H, J=19.0 Hz, J'=7.5 Hz, 3'-H), 3.16 (dd, 1H, J=19.0 Hz, J'=7.5 Hz, 3'-H), 3.88 (dd, 1H, J=11.5 Hz, J'=4.0 Hz, 5'-H), 4.02 (dd, 1H, J=11.5 Hz, J'=3.5 Hz, 5'-H), 4.66 (dddd, 1H, J=J'=7.5 Hz, J"=4.0 Hz, J' "=3.5 Hz, 4'-H), 6.06, (s, 1H, 1'-H), 7.52 (m, 2H, m-C6H5), 7.61 (m, 1H, p-C6H5), 8.02 (m, 2H, o-C6H5), 8.11, 8.78 (2s, 2H, 2-H, 8-H), 9.03 (bs, 1H, NH) DCI/NH3MS, m/z 468 (M+H)+, 240; exact mass calcd for C23H30N5O4Si (M+H)+ : 468.2067, found: 468.2067.

Workup

  1. additionFifteen minutes after the final addition
  2. washwashed with water
  3. extractionThe aqueous phase was extracted several times with dichloromethane
  4. dry with materialthe combined organic extracts dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6348f0765eba42cf919d126959f47995
Source dataset
uspto-grants-1995_05
Patent number
US05420276

Reaction notes

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