Tetrahydrofuran → HCID 68957797, compound

HRID 2378045Notes

Reaction equation

HRID 2378045 reaction equation
[C:1]([Si:5]([CH3:24])([CH3:23])[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=[N:21][OH:22])[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C1COCC1.C([Li])CCC.[CH3:35][O:36][C:37]([C:39]1([C:42](OC)=[O:43])[CH2:41][CH2:40]1)=[O:38]>CCCCCC>[CH3:35][O:36][C:37]([C:39]1([C:42]2([OH:43])[O:22][N:21]=[C:13]([C:10]3[CH:11]=[CH:12][C:7]([O:6][Si:5]([C:1]([CH3:2])([CH3:4])[CH3:3])([CH3:24])[CH3:23])=[CH:8][CH:9]=3)[CH:14]2[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:41][CH2:40]1)=[O:38]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 27695391,1-Cyclopropanedicarboxylic acid, 1,1-dimethyl esterHCID 72579577HCID 72579577, compound2×HCID 178418339Butyllithium2×

Product 1

HCID 68957797HCID 68957797, compound

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent2×

Conditions

Temperature
-9 °C

Procedure

An oven-dried 1 L three-neck flask equipped with magnetic stir bar, nitrogen gas inlet valve, and digital thermometer probe, and addition funnel had been charged with 1-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-2-phenyl-ethanone oxime (Compound B, 26.6 g) and anhydrous THF (140 mL.) The reaction vessel is submerged in an ice-methanol bath equipped with a thermometer reading −18° C. The internal solution temperature is cooled to −9.0° C. A solution consisting of 2.5 M n-butyllithium in hexane (31 mL, 78 mmol) is added dropwise over 25 minutes (bath temperature −18 to −16° C., internal mixture temperature −9.0 to −0.6° C.), over which time the solution color turned from yellow after addition of the first few drops to orange at the first endpoint. The reaction mixture is stirred for three minutes as the internal mixture temperature cooled to −3.3° C. (bath temperature −14° C.) Another 31 mL of 2.5 M n-butyllithium in hexane is added over 11 minutes (bath temperature −14 to −16° C., internal mixture temperature −3.3 to −0.3° C. with a peak temperature in that time period of +0.2° C.) The reaction mixture is stirred for 31 minutes as the internal mixture temperature cooled to −10.1° C. (bath temperature −14° C.) Cyclopropane-1,1-dicarboxylic acid dimethyl ester (26.0 mL) is added over less than one minute to give an internal mixture temperature of +4.6° C. (bath temperature −13° C.) The reaction mixture is stirred for one hour and is quenched with the addition of brine solution (100 mL.) The layers are separated and the organic phase is dried over anhydrous magnesium sulfate and is concentrated under reduced pressure to afford an oil (59.9 g.) The product is purified by flash silica gel column chromatography to afford the foam product (24.0 g.)

Workup

  1. customAn oven-dried 1 L three-neck flask equipped with magnetic stir bar, nitrogen gas inlet valve
  2. additiondigital thermometer probe, and addition funnel
  3. customis submerged in an ice-methanol bath
  4. customequipped with
  5. customa thermometer reading −18° C
  6. additionis added dropwise over 25 minutes (bath temperature −18 to −16° C., internal mixture temperature −9.0 to −0.6° C.)
  7. additionyellow after addition of the first few drops to orange at the first endpoint
  8. additionis added over 11 minutes (bath temperature −14 to −16° C., internal mixture temperature −3.3 to −0.3° C. with a peak temperature in that time period of +0.2° C.) The reaction mixture
  9. stirringis stirred for 31 minutes as the internal mixture temperature
  10. additionis added over less than one minute
  11. customto give an internal mixture temperature of +4.6° C. (bath temperature −13° C.) The reaction mixture
  12. stirringis stirred for one hour
  13. customis quenched with the addition of brine solution (100 mL.) The layers
  14. customare separated
  15. dry with materialthe organic phase is dried over anhydrous magnesium sulfate
  16. concentrationis concentrated under reduced pressure
  17. customto afford an oil (59.9 g.) The product
  18. customis purified by flash silica gel column chromatography
  19. customto afford the foam product (24.0 g.)

Sources & evidence

ORD record
ord-4c6464bb61ca4c768a60a9d8c37164ab
Source dataset
uspto-grants-2008_12
Patent number
US07470715B2

Reaction notes

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