Triphenylphosphine → 3-[6-(6-Chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethoxy]isoxazole-5-carboxylic acid methyl ester

HRID 549777Notes

Reaction equation

HRID 549777 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:11]1[CH:15]2[O:16][C:17]([CH3:20])([CH3:19])[O:18][CH:14]2[CH:13]([CH2:21][OH:22])[O:12]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:42][O:43][C:44]([C:46]1[O:50][N:49]=[C:48](O)[CH:47]=1)=[O:45].CCOC(/N=N/C(OCC)=O)=O>ClCCl>[CH3:42][O:43][C:44]([C:46]1[O:50][N:49]=[C:48]([O:22][CH2:21][CH:13]2[CH:14]3[CH:15]([O:16][C:17]([CH3:19])([CH3:20])[O:18]3)[CH:11]([N:6]3[CH:5]=[N:4][C:3]4[C:7]3=[N:8][CH:9]=[N:10][C:2]=4[Cl:1])[O:12]2)[CH:47]=1)=[O:45]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 4206947[4-(6-Chloropurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanolHCID 5462977Diethyl azodicarboxylateHCID 178498603HCID 178498603, compound

Product 1

HCID 865997133-[6-(6-Chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethoxy]isoxazole-5-carboxylic acid methyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of [6-(6-Chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-methanol (0.570 g, 1.74 mmol) in 16 mL of dry dichloromethane was added polymer-bound triphenylphosphine (PS-TPP; Argonaut Tech., 2.14 mmol/g, 0.91 g, 1.2 eq), followed by methyl-3-hydroxy-5-isoxazolecarboxylate (0.248 g, 1 eq). The mixture was sonicated for 15 minutes then stirred at room temperature for 1 h under argon. The reaction mixture was cooled to 0° C. and under argon flow diethylazodicarboxylate (0.33 g, 1.1 eq), dissolved in 1 ml of dichloromethane, was added dropwise via syringe. The mixture was protected from light and stirred at 0° C. for 30 min. then at room temperature for 20 h. The resin was washed liberally with dichloromethane and methanol. The organic solution obtained from the washes was concentrated to give, after flash chromatography purification, 0.740 g of the product as a white solid (95% yield). 1H NMR (300 MHz, CDCl3) δ 8.76 (s, 1H), 8.23 (s, 1H), 6.42 (s, 1H), 6.23 (d, J=2.1 Hz, 1H), 5.43 (dd, J=2.1 Hz, 1H), 5.14 (dd, J=3.6 Hz, 1H), 4.7 (m, 1H), 4.61 (dd, J=3.9 Hz, 1H), 4.49 (dd, J=5.7 Hz, 1H), 3.93 (s, 3H), 1.65 (s, 3H), 1.42 (s, 3H). MW calculated for C18H18ClN5O7 (MH+) 452. found 452 by LCMS.

Workup

  1. customThe mixture was sonicated for 15 minutes
  2. additionwas added dropwise via syringe
  3. stirringstirred at 0° C. for 30 min.
  4. waitat room temperature for 20 h
  5. washThe resin was washed liberally with dichloromethane and methanol
  6. customThe organic solution obtained from the washes
  7. concentrationwas concentrated
  8. customto give

Sources & evidence

ORD record
ord-ff6dfb0268c648fd9001fe9cf701540b
Source dataset
uspto-grants-2011_05
Patent number
US07943760B2

Reaction notes

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