HCID 14729338, compound → 2-(Tetrahydro-6-hydroxy-2,2dimethylfuro[2,3-d]-l,3-dioxol-5-yl)-3-pyrrolidinol

HRID 974084Notes

Reaction equation

HRID 974084 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH:7][CH:8]1[CH:12]([CH:13]2[O:22][CH:16]3[O:17][C:18]([CH3:21])([CH3:20])[O:19][CH:15]3[CH:14]2[OH:23])[NH:11][C:10](=O)[CH2:9]1>O1CCCC1>[OH:23][CH:14]1[CH:15]2[CH:16]([O:17][C:18]([CH3:21])([CH3:20])[O:19]2)[O:22][CH:13]1[CH:12]1[CH:8]([OH:7])[CH2:9][CH2:10][NH:11]1

Participants

4

Reactant 2

HCID 14729338HCID 14729338, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 147293412-(Tetrahydro-6-hydroxy-2,2dimethylfuro[2,3-d]-l,3-dioxol-5-yl)-3-pyrrolidinolYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a well-stirred, nitrogen-blanketed suspension of lithium aluminum hydride (2.3 g, 60.0 mmol) in anhydrous tetrahydrofuran (150 mL), lactam IV (3.0 g, 11.5 mmol) was added in portions during 3-5 min at 25° C. Caution: foaming and H2 evolution. This mixture was refluxed for 20 h then cooled to 0°-5° C. and the reaction quenched by the careful, sequential addition of water (2.5 mL), lN NaOH (2.5 mL) and water 7.5mL). This mixture was stirred at about 5° C. for 20 min then filtered through a pad of Celite. The collected aluminate salts were washed with tetrahydrofuran (200 mL) and the combined filtrate and wash was concentrated to dryness at reduced pressure, leaving 1.7g of [3aR[3aα,5α(2R*,3S*),6e,6aα]]-2-(Tetrahydro-6-hydroxy-2,2-dimethylfuro[2,3-d]-l,3-dioxol-5-yl)-3-pyrrolidinol (V) as a white powder. The collected aluminate salts were refluxed with 100 mL of tetrahydrofuran-water (9:1) for 45 min. The salts were filtered, washed with tetrahydrofuran (50 mL) and the combined filtrate evaporated to dryness, leaving 0.5 g more of V for a total yield of 77%. An analytical sample was obtained as fine, colorless needles by recrystallization from methanol mp 223°-225° C. (dec); [α]D 25=-5.0 (c 0.32, H2O); 1H NMR (CDCl3) δ5.92 (d, 1, J=3.8 Hz, H-1), 4.55 (d, 1, J=3.8 Hz, H-2), 4.40 (ddd, J=5.3, 3.6, l.6Hz, H-6), 4.25 (d, 1, J=2.6Hz, H-3), 4.13 (dd, 1, J=7.8, 2.6Hz, H-4), 3.50 (m, 3, OH, NH), 3.18 (ddd, 1, J-11.2, 7.8, 7.6Hz, H-8'), 3.12 (dd, 1, J=7.8, 3.6Hz, H-5), 2.86 (ddd, 1, J=ll.2, 9.5, 5.lHz, H-8), 2.05 (dddd, J=l3.8, 9.5, 7.6, 5.3Hz, H-7'), 5 1.86 (dddd, J=l3.8, 7.8, 5.1, l.6Hz, H-7), 1.50 [s, 3, CH3), 1.32 (s, 3, CH3); 13C NMR δ26.1, 26.6, 35.4, 43.2, 61.6, 70.6, 75.6, 77.9, 85.3, 103.8, 110.1; mass spectrum, m/z(rel intensity) 246 (MH+,l00), 188 (MH+ -C3H6O, 52).

Workup

  1. additionwas added in portions during 3-5 min at 25° C
  2. temperatureThis mixture was refluxed for 20 h
  3. temperaturethen cooled to 0°-5° C.
  4. customthe reaction quenched by the careful,
  5. additionsequential addition of water (2.5 mL), lN NaOH (2.5 mL) and water 7.5mL)
  6. filtrationthen filtered through a pad of Celite
  7. washThe collected aluminate salts were washed with tetrahydrofuran (200 mL)
  8. washthe combined filtrate and wash
  9. concentrationwas concentrated to dryness at reduced pressure

Sources & evidence

ORD record
ord-c5fe98478b0444159af95dd325a0a630
Source dataset
uspto-grants-1991_11
Patent number
US05066807

Reaction notes

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