Ammonia → HCID 69912128, compound

HRID 353701

Reaction equation

HRID 353701 reaction equation
[Li].Br[CH2:3][CH3:4].C([Li])C.[CH3:8][C:9]([Si:12]([CH3:34])([CH3:33])[O:13][C@H:14]1[CH2:19][CH2:18][C@H:17]2[C@H:20]3[C@H:29]([CH2:30][CH2:31][C@:15]12[CH3:16])[C@@H:28]1[C:23](=[CH:24][C:25](=[O:32])[CH2:26][CH2:27]1)[CH:22]=[CH:21]3)([CH3:11])[CH3:10].Cl[Si:36]([CH3:39])([CH3:38])[CH3:37].[Cl-].[NH4+].N>O1CCCC1.[Cu]I.C(OCC)C>[CH3:11][C:9]([Si:12]([CH3:34])([CH3:33])[O:13][C@H:14]1[CH2:19][CH2:18][C@H:17]2[C@H:20]3[C@H:29]([CH2:30][CH2:31][C@:15]12[CH3:16])[C@@H:28]1[C:23]([CH:24]=[C:25]([O:32][Si:36]([CH3:39])([CH3:38])[CH3:37])[CH2:26][CH2:27]1)=[CH:22][C@H:21]3[CH2:3][CH3:4])([CH3:8])[CH3:10]

Participants

11

Reactant 7

HCID 222AmmoniaHCID 6332Ethyl BromideHCID 6397ChlorotrimethylsilaneHCID 25517Ammonium ChlorideHCID 3028194LithiumHCID 57001014HCID 57001014, compoundHCID 178506846HCID 178506846, compound

Product 1

HCID 69912128HCID 69912128, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

i)—A mixture of lithium (0.647 g) and dry diethyl ether (26 ml) was cooled to −30° C. Bromoethane (3.45 ml) was added dropwise while maintaining the temperature below −25° C. After 30 min. stirring at −30° C. the solution of ethyllithium was added dropwise to a suspension of copper(I) iodide (4.0 g) in dry tetrahydrofuran (40 ml), cooled to −40° C. The resulting cuprate solution was stirred at −30° C. for 30 min. and a solution of (17β)-17-[[(1,1-dimethylethyl)dimethylsilyl]oxy]estra-4,6-dien-3-one [Nickisch, K. et al, Tetrahedron Lett. 29, 1533 (1988); 2.5 g] in dry tetrahydrofuran (20 ml) was added dropwise. Stirring was continued at −30° C. for 30 min., chlorotrimethylsilane (2.58 ml) was added and stirring was continued for another 30 min. The reaction mixture was poured into a mixture of a saturated aqueous solution of ammonium chloride and concentrated ammonia (9:1). The product was extracted into ethyl acetate; the combined organic phases were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine, dried over magnesium sulfate and concentrated under reduced pressure, to give (7α,17β)-17-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-7-ethyl-3-[(trimethylsilyl)oxy]estra-3,5-diene (2.81 g). The product was used in the following step without further purification.

Workup

  1. temperaturewhile maintaining the temperature below −25° C
  2. temperaturecooled to −40° C
  3. stirringstirring
  4. waitwas continued for another 30 min
  5. extractionThe product was extracted into ethyl acetate
  6. washthe combined organic phases were washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-60e10129d2a849bfb27ccdf61e4da269
Source dataset
uspto-grants-2004_06
Patent number
US06756366B1

Linked notes

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