Sodium hydride → HCID 66960144, compound

HRID 1367745Notes

Reaction equation

HRID 1367745 reaction equation
[CH2:1]([C:3]1[C:19]([O:20][CH2:21][O:22][CH3:23])=[CH:18][C:17]2[CH2:16][CH2:15][CH:14]3[CH:6]([CH2:7][CH2:8][C:9]4([CH3:25])[CH:13]3[CH2:12][CH2:11][CH:10]4[OH:24])[C:5]=2[CH:4]=1)[CH3:2].[H-].[Na+].[CH3:28][O:29][CH2:30][CH2:31]Br.[Cl-].[NH4+]>C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH2:1]([C:3]1[C:19]([O:20][CH2:21][O:22][CH3:23])=[CH:18][C:17]2[CH2:16][CH2:15][CH:14]3[CH:6]([CH2:7][CH2:8][C:9]4([CH3:25])[CH:13]3[CH2:12][CH2:11][CH:10]4[O:24][CH2:31][CH2:30][O:29][CH3:28])[C:5]=2[CH:4]=1)[CH3:2]

Participants

7

Reactant 4

HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 809722-Bromoethyl methyl ether2×HCID 66960124HCID 66960124, compound

Product 1

HCID 66960144HCID 66960144, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A toluene (10 mL) solution of 2-Et-3-O-MOM estradiol 53 (170 mg, 0.5 mmol) was treated with sodium hydride (80 mg, 2 mmol) and then brought to reflux for 0.5 h prior to addition of 2-(methoxy)ethyl bromide (141 μL, 1.5 mmol). The reaction was refluxed for 14 h then treated with further aliquots of sodium hydride (80 mg, 2 mmol) and 2-(methoxy)ethyl bromide (141 μL, 1.5 mmol) before refluxing for a further 8 hours after which time no residual starting material remained. The reaction was then cooled to room temperature, diluted in ethyl acetate (30 mL) and then treated with saturated ammonium chloride (20 mL). The organic layer were separated, washed with water (2×20 mL), brine, dried and evaporated. The desired ether 54, a clear colourless oil (128 mg, %) was isolated by column chromatography (gradient 0 to 20% ethyl acetate in hexane) and showed δH (400 MHz, CDCl3, ref. TMS=0) 7.08 (1H, s, ArH), 6.78 (1H, s, Ar, H), 5.17 (2H, s, OCH2), 3.67-3.74 (1H, m), 3.52-3.56 (2H, m), 3.48 (3H, s, OMe), 3.43 (1H, dd, J 8.6 and 8.2, CHO), 3.40 (3H, s, OMe), 2.78-2.86 (2H, m, 6-CH2), 2.63 (2H, q, J 7.4, CH2Me), 2.37-2.44 (1H, m), 2.14-2.22 (1H, m), 2.01-2.11 (2H, m), 1.83-1.90 (1H, m), 1.23-1.72 (8H, m), 1.19 (3H, t, J 7.4, CH2Me) and 0.81 (3H, s, 18-CH3) δC 152.6, 135.0, 133.2, 130.3, 126.1, 114.0, 94.3, 89.6, 72.3, 69.6, 59.2, 56.0, 50.4, 44.1, 43.5, 38.7, 38.3, 29.7, 28.3, 27.4, 26.6, 23.6, 23.2, 15.0 and 11.7.

Workup

  1. temperatureto reflux for 0.5 h
  2. temperatureThe reaction was refluxed for 14 h
  3. temperaturebefore refluxing for a further 8 hours after which time
  4. customThe organic layer were separated
  5. washwashed with water (2×20 mL), brine
  6. customdried
  7. customevaporated

Sources & evidence

ORD record
ord-ddee306bcde04ff0a19d6f43034e8e80
Source dataset
uspto-grants-2011_02
Patent number
US07893284B2

Reaction notes

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