Ethyl Acetate → HCID 58013238, compound

HRID 1799452Notes

Reaction equation

HRID 1799452 reaction equation
COCCO[AlH2-]OCCOC.[Na+].[CH2:13]([O:20][C@:21]1([CH3:44])[C@H:25]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:24]([CH2:34][O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:23][C:22]1=[O:43])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[CH2:13]([O:20][C@:21]1([CH3:44])[C@H:25]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:24]([CH2:34][O:35][CH2:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[O:23][CH:22]1[OH:43])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 16684438Red-Al2×HCID 57755415HCID 57755415, compound

Product 1

HCID 58013238HCID 58013238, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-40 °C

Procedure

Vitride (22 L, 76.19 mole, 70% wt. in toluene, 3.46M) was diluted with toluene (18 L) and added dropwise to a solution of (3R,4R,5R)-3,4-bis(benzyloxy)-5-(benzyloxymethyl)-3-methyl-dihydrofuran-2(3H)-one (62.5 mole from step 1) in toluene (150 L) maintaining temperature around −40±5° C. during the addition. After the addition was over, TLC was checked to ensure completion of the reaction (if the reaction is not complete, more Vitride is added till reaction is complete). The reaction was quenched with acetone (5.5 L) maintaining temperature between −30° C. and −40° C. and 2.5 N HCl (70 L) was added at 0° C. The toluene layer was separated and the aqueous layer was extracted with ethyl acetate (30 L). The combined organic layers were washed with brine (30 L), dried over magnesium sulfate (10 Kg), filtered and the filtrate was concentrated in vacuo to dryness to furnish 32 kg of crude residue. The crude material was used as such for the next step. An analytical sample was prepared by purification of 1 g of residue by flash column chromatography (silica gel, ethyl acetate in hexane) to furnish (3R,4R,5R)-3,4-bis(benzyloxy)-5-(benzyloxymethyl)-3-methyl-tetrahydrofuran-2-ol. 1HNMR (DMSO-d6): δ 7.35-7.24 (m, 15 H), 6.68 (d, J=5 Hz, 0.6 H), 5.89 (d, J=6.8 Hz, 0.4 H), 5.00 (m, 1 H), 4.73-4.50 (m, 6 H), 4.18-4.13 (m, 0.4 H), 4.06-4.00 (m, 0.6 H), 3.79 (d, J=7.5 Hz, 0.6 H), 3.65 (d, J=6 Hz, 0.4 H), 3.61-3.48 (m, 2 H), 1.33 (s, 2 H), 1.32 (s, 1 H); MS (ES+): 457.38 (100% M+Na). Analysis: Calculated for C27H30O5: C, 74.62; H, 6.96; Found: C, 74.36; H, 7.05.

Workup

  1. additionduring the addition
  2. additionAfter the addition
  3. customcompletion of the reaction (if the reaction
  4. customThe reaction was quenched with acetone (5.5 L)
  5. temperaturemaintaining temperature between −30° C. and −40° C. and 2.5 N HCl (70 L)
  6. additionwas added at 0° C
  7. customThe toluene layer was separated
  8. extractionthe aqueous layer was extracted with ethyl acetate (30 L)
  9. washThe combined organic layers were washed with brine (30 L)
  10. dry with materialdried over magnesium sulfate (10 Kg)
  11. filtrationfiltered
  12. concentrationthe filtrate was concentrated in vacuo to dryness
  13. customto furnish 32 kg of crude residue

Sources & evidence

ORD record
ord-ea40c781fdbb47a1b9bb27efb4e3ab8b
Source dataset
uspto-grants-2013_01
Patent number
US08344132B2

Reaction notes

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