Tetraethylammonium fluoride hydrate → HCID 10955403, compound

HRID 1684704Notes

Reaction equation

HRID 1684704 reaction equation
C([Si]1(C(C)C)[O:11][C@H:10]2[CH2:12][C@H:13]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][C@@H:9]2[CH2:8][O:7][Si](C(C)C)(C(C)C)O1)(C)C.O.[F-].C([N+](CC)(CC)CC)C>O1CCCC1>[OH:11][C@@H:10]1[C@@H:9]([CH2:8][OH:7])[CH2:14][C@@H:13]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:20])([CH3:19])[CH3:21])[CH2:12]1

Participants

4

Reactant 2

HCID 16211652Tetraethylammonium fluoride hydrateHCID 86751004HCID 86751004, compound

Product 1

HCID 10955403HCID 10955403, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (-)-(6aR, 8R, 9aS)-tert-butyl N-(hexahydro-2,2,4,4-tetraisopropylcyclopenta [f]-1,3,5,2,4-trioxadisilocin-8-yl)carbamate(74.32 g, 0.1569 mol, corresponding to the first portion of product in the above Example) in tetrahydrofuran (300 mL) was added tetraethyl ammonium fluoride hydrate (24.62 g, about 0.15 mol, Aldrich). The lumps of solid were broken up, the mixture was degassed (nitrogen), then refluxed for 45 minutes. After cooling to room temperature, the reaction mixture was applied to a column of silica gel (200 g) and eluted with tetrahydrofuran (3 L). The eluate was concentrated under vacuum to an amber oil, which was taken up in hexanes (150 mL). Crystallization began spontaneously, and was allowed to continue at -5° for two days. The crystals of crude title compound were collected by filtration, washed sparingly with 10% ethyl acetate-hexanes, and dried by suction to constant weight (25.08 g, 0.1084 mol). The procedure was repeated on the second portion of product from the above Example (73.82 g, 0.1558 mol), giving additional crude title compound (27.28 g, 0.1180 mol). The two portions of crude title compound were combined and recrystallized from boiling ethyl acetate (250 mL), giving white crystals of the title compound (46.67 g., 0.2018 mol, 53.7% of theoretical from the triol product of Example 5) having the following characteristics: m.p. 126-127.9° C.; 1H-NMR (DMSO-d6), δ: 6.75 (dr d, J=7.8 Hz, 1H, NH), 4.49 (t, J=4.5 Hz, CH2OH) overlapping 4.47 (d,J=4.3 Hz, CHOH) with total integration of 2H, 3.80-3.93 (m, 2H, CHN and CHOH), 3.34 (m, w1/2=20 Hz, CH2OH), 2.25 (dt, 1H, CHCH2), 1.79-1.63 (m, 2H, CH2CHOH), 1.63-1.50 (m, 1H, 1/2CH2), 1.38 (s, 9H, C(CH3)3), 1.11-0.96 (m, 1H, 1/2CH2); Cl-MS (CH4): 232(M+1).

Workup

  1. customthe mixture was degassed (nitrogen)
  2. temperaturerefluxed for 45 minutes
  3. washeluted with tetrahydrofuran (3 L)
  4. concentrationThe eluate was concentrated under vacuum to an amber oil, which
  5. customCrystallization
  6. filtrationThe crystals of crude title compound were collected by filtration
  7. washwashed sparingly with 10% ethyl acetate-hexanes
  8. customdried by suction to constant weight (25.08 g, 0.1084 mol)
  9. customgiving additional crude title compound (27.28 g, 0.1180 mol)
  10. customrecrystallized

Sources & evidence

ORD record
ord-9fb80897ea2f4d59bf984726ccebb688
Source dataset
uspto-grants-1997_06
Patent number
US05641889

Reaction notes

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