Ethyl Bromide → HCID 54757324, compound

HRID 548546Notes

Reaction equation

HRID 548546 reaction equation
[Li][CH2:2][CH2:3]CC.C(NC(C)C)(C)C.[C:13]([C@H:15]([CH3:35])[C@@H:16]1[C@:24]2([CH3:25])[C@H:19]([C@@H:20]([O:26][C:27](=[O:34])[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:21][CH2:22][CH2:23]2)[CH2:18][CH2:17]1)#N.CCBr.[NH4+:39].[Cl-]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[C:13]([C@@:15]([C@@H:16]1[C@:24]2([CH3:25])[C@H:19]([C@@H:20]([O:26][C:27](=[O:34])[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:21][CH2:22][CH2:23]2)[CH2:18][CH2:17]1)([CH3:35])[CH2:2][CH3:3])#[N:39]

Participants

8

Reactant 5

HCID 6332Ethyl BromideHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 86615576HCID 86615576, compoundHCID 178418339Butyllithium

Product 1

HCID 54757324HCID 54757324, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
0 °C

Procedure

n-BuLi (1.6 M in hexanes, 1.0 mL, 1.6 mmol) was added at 0° C. to the flask containing diisopropylamine (262 μL, 1.54 mmol) and THF (2 mL). The solution was stirred at 0° C. for 20 min., cooled to −78° C. and siphoned to the solution of 2 (430 mg, 1.31 mmol) in THF (1.5 mL). The resulted yellow mixture was stirred for 30 min, then HMPA (600 μL) was added and stirring was continued for another 15 min. Then CH3CH2Br (310 μL, 4.08 mmol) was added, and the solution was stirred at −78° C. for 40 min. Saturated NH4Cl was added and the mixture was extracted with ethyl acetate. The combined organic phases were washed with water, dried (MgSO4) and evaporated. The residue was applied on a silica column. Elution with hexane/ethyl acetate (95:5) resulted in pure compound 3 (280 mg, 60%; 80% based on recovered substrate). Further elution with hexane/ethyl acetate (95:5) gave unreacted 2 (107 mg). 3: [α]24D+117.5° (c 0.2 CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.023 (3H, t, J=7.4 Hz, 23-H3), 1.337 (3H, s, 18-H3), 1.397 (3H, s, 21-H3), 2.14 (1H, br d, J=12.9 Hz, 9β-H), 5.40 (1H, narr m, 8α-H), 7.45 (2H, t, J=7.4 Hz, Ar), 7.57 (1H, t, J=7.4 Hz, Ar), 8.05 (2H, d, J=7.4 Hz, Ar).

Workup

  1. temperaturecooled to −78° C.
  2. stirringThe resulted yellow mixture was stirred for 30 min
  3. stirringstirring
  4. waitwas continued for another 15 min
  5. stirringthe solution was stirred at −78° C. for 40 min
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe combined organic phases were washed with water
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. washElution with hexane/ethyl acetate (95:5)

Sources & evidence

ORD record
ord-add5890ae4b3466db853f74197e02d6b
Source dataset
uspto-grants-2011_05
Patent number
US07943601B2

Reaction notes

Loading…