Diisopropylamine → 4-(4-(4-Bromo-2-fluorophenoxy)phenoxy)-3-hydroxypentanoate ethyl ester

HRID 4465Notes

Reaction equation

HRID 4465 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14].[Br:19][C:20]1[CH:37]=[CH:36][C:23]([O:24][C:25]2[CH:35]=[CH:34][C:28]([O:29][CH:30]([CH3:33])[CH:31]=[O:32])=[CH:27][CH:26]=2)=[C:22]([F:38])[CH:21]=1.[NH4+].[Cl-]>CCOCC.CCCCCC>[CH2:17]([O:16][C:13](=[O:15])[CH2:14][CH:31]([OH:32])[CH:30]([O:29][C:28]1[CH:34]=[CH:35][C:25]([O:24][C:23]2[CH:36]=[CH:37][C:20]([Br:19])=[CH:21][C:22]=2[F:38])=[CH:26][CH:27]=1)[CH3:33])[CH3:18]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 13880897HCID 13880897, compoundHCID 178418339Butyllithium

Product 1

HCID 201526024-(4-(4-Bromo-2-fluorophenoxy)phenoxy)-3-hydroxypentanoate ethyl esterYield 70%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8058HexaneSolvent

Procedure

A solution of 1.54 ml (11 mmol) of diisopropylamine in 20 ml of ether was cooled under N2 to -78° C. and 6.9 ml (11 mmol) of 1.6M n-butyllithium in hexane was slowly added. After 15 min of -78° C. 0.97 g (11 mmol) of ethyl acetate in 3 ml of ether was added dropwise. The resulting mixture was stirred at -78° C. for 15 min when a solution of 3.39 g (10 mmol) of 2-(4-(4-bromo-2-fluorophenoxy)phenoxy)propanaldehyde in 5 ml of ether was slowly added. The mixture was allowed to warm to room temperature, poured into aqueous NH4Cl and the aqueous phase separated and extracted with ether. The combined organic layers were dried over MgSO4 and evaporated to dryness and the residue purified by prep LC, eluting with 85:15 hexane:acetone. The resulting colorless oil was thoroughly dried to leave 2.99 g of product. Structure was confirmed by IR and NMR analysis. Calc. for C17H20BrFO5 : C, 53.41, H, 4.72. Found: C, 53.10, H, 4.66.

Workup

  1. additionwas slowly added
  2. customthe aqueous phase separated
  3. extractionextracted with ether
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. customevaporated to dryness
  6. customthe residue purified by prep LC
  7. washeluting with 85:15 hexane
  8. customThe resulting colorless oil was thoroughly dried

Sources & evidence

ORD record
ord-203e66a3104e4a1aa4c270e295862ca4
Source dataset
uspto-grants-1988_02
Patent number
US04725683

Reaction notes

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