tert-Butyl bromoacetate → HCID 68675115, compound

HRID 1993067Notes

Reaction equation

HRID 1993067 reaction equation
[CH3:1][O:2][C:3](=[O:29])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:14]=[C:15]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)[CH:16]=[CH:17][CH:18]=2)=[CH:7][CH:6]=1.[Li+].CC([N-]C(C)C)C.Br[CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41]>C1COCC1>[CH3:1][O:2][C:3](=[O:29])[CH:4]([C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:12][C:13]2[CH:14]=[C:15]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:26])([F:28])[F:27])=[CH:21][CH:20]=3)[CH:16]=[CH:17][CH:18]=2)=[CH:9][CH:10]=1)[CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41]

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 2724682Lithium diisopropylamideHCID 68675484HCID 68675484, compound

Product 1

HCID 68675115HCID 68675115, compoundYield 64.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

Compound 50.1 (4 g, 10 mmol) in THF (12 mL) was added dropwise to LDA in THF (1M, 12 mL) at −78° C. The resulting mixture was stirred for 30 min. before tert-butyl bromoacetate (2.15 g, 11 mmol) in THF (2 mL) was added over 10 min. The reaction mixture was stirred for 2 h at −78° C. and allowed to warm slowly to 0° C. The reaction was quenched with saturated aqueous NH4Cl (20 mL). The organic phase was extracted with ethyl acetate (25 mL×3). The organic extracts were combined, dried over MgSO4 and concentrated under reduced pressure. The resulting residue was purified via flash chromatography (50% ethyl acetate in hexanes) to yield 3.3 g of 50.2. MS ESI (pos.) m/e: 537 (M+Na). 1H NMR (400 MHz) (CDCl3) δ 7.72 (4H, s); 7.68 (1H, s); 7.58-7.49 (3H, m); 7.25-7.24 (2H, m); 6.98-6.97 (2H, m); 5.14 (2H, s); 4.04-4.0 (1H, m); 3.7 (3H, s); 3.1 (1H, m); 2.63 (1H, m); 1.42 (9H, s).

Workup

  1. additionwas added over 10 min
  2. temperatureto warm slowly to 0° C
  3. customThe reaction was quenched with saturated aqueous NH4Cl (20 mL)
  4. extractionThe organic phase was extracted with ethyl acetate (25 mL×3)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified via flash chromatography (50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-2c3507b6440e40e9a157122ca9dadd1f
Source dataset
uspto-grants-2010_01
Patent number
US07649110B2

Reaction notes

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