Sulfuric Acid → HCID 13294648, compound

HRID 1746631Notes

Reaction equation

HRID 1746631 reaction equation
CO[C:3](OC)([CH3:5])[CH3:4].[O:8]=[CH:9][C@@H:10]([C@@H:12]([C@@H:14]([CH2:16][OH:17])[OH:15])[OH:13])[OH:11].C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2-]C(C)=O.O=C[C@@H]([C@@H]([C@@H](CO)O)O)O.OS(O)(=O)=O.C(N(CC)CC)C>C(O)C.ClCCl.C(O)C.CC(C)=O>[OH:8][CH2:9][CH:10]1[C@H:12]2[O:13][C:3]([CH3:5])([CH3:4])[O:15][C@H:14]2[CH:16]([OH:17])[O:11]1

Participants

10

Reactant 6

HCID 1118Sulfuric AcidHCID 6101p-Toluenesulfonic acidHCID 64952,2-DimethoxypropaneHCID 8471TriethylamineHCID 5311110Aldehydo-D-ribose4×HCID 178521087HCID 178521087, compound2×

Product 1

HCID 13294648HCID 13294648, compound

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 702EthanolSolventHCID 21584144Dichloromethane ethanolSolvent

Procedure

Into a 2000 L reactor was charged acetone (1200 L) and 2,2-dimethoxypropane (125 kg, 1200 mol, 1.2 eq), followed by D-ribose (150 kg, 999 mol). The mixture was stirred at ambient temperature. p-TSA (p-toluene sulfonic acid) (9.6 kg, 49.5 mol, 0.05 eq) was added in portions over 40 minutes. The reaction mixture was heated at 30° C. and monitored by TLC every hour. After 14 hours, TLC indicated complete conversion. A sample from the reaction mixture and standard samples for ribose and ribose acetonide were applied to a commercial silica gel TLC plate, and the plate was run in the mobile phase dichloromethane/ethanol=8:1. The plate was then sprayed with 10% H2SO4 in ethanol and heated using a heat gun. Ribose-related compounds gave dark spots on the plate. The Rf for Ribose was ˜0.1, while Rf for ribose acetonide (1) was usually 0.3˜0.35. To the reaction mixture was added triethylamine (8.1 kg, 0.08 eq). Acetone was distilled under vacuum (water bath temperature<60° C.) over 12 hours. The residue was diluted with dichloromethane (300 L). The mixture was stirred for 0.5 hour at ambient temperature, and then solvent was removed under vacuum over 4 hours. This operation was repeated once, and the residue was used in next step without further purification. 1H NMR (400 MHz, CD3OD) δ 1.31 (s, 3H, CH3), 1.44 (s, 3H, CH3), 3.59 (dd, J=5.6, 12.0 Hz, 1H, HOCHH), 3.63 (dd, J=4.8, 12.0 Hz, 1H, HOCHH), 4.19 (irregular t, J=4.4, 5.2 Hz, 1H, 4-H), 4.52 (d, J=6.0 Hz, 1H, 3-H), 4.77 (d, J=6.0 Hz, 1H, 2-H), 5.26 (s, 1H, anomeric H). Anal. calcd for C8H14O5: C, 50.52; H, 7.42. Found: C, 50.48; H, 7.36; [α]25D−36.2 (c 1.45, acetone) [lit., [α]25D−37 (c 0.53, acetone)].

Workup

  1. temperatureThe reaction mixture was heated at 30° C.
  2. waitmonitored by TLC every hour
  3. temperatureheated
  4. customgave dark spots on the plate
  5. distillationAcetone was distilled under vacuum (water bath temperature<60° C.) over 12 hours
  6. additionThe residue was diluted with dichloromethane (300 L)
  7. stirringThe mixture was stirred for 0.5 hour at ambient temperature
  8. customsolvent was removed under vacuum over 4 hours
  9. customthe residue was used in next step without further purification

Sources & evidence

ORD record
ord-4a041255221d406c90751090ee2f4956
Source dataset
uspto-grants-2015_10
Patent number
US09150520B2

Reaction notes

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