tert-Butyl bromoacetate → HCID 86587571, compound

HRID 481252Notes

Reaction equation

HRID 481252 reaction equation
[NH:1]([C:8]([C@H:10]1[N:14]2[C:15](=[O:37])[C:16]([N:19]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:20](=[O:29])[O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:17][N:18]=[C:13]2[CH2:12][CH2:11]1)=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:49][C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51]>C1COCC1>[NH:1]([C:8]([C@H:10]1[N:14]2[C:15](=[O:37])[C:16]([N:19]([CH2:30][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:20]([O:21][CH2:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[O:29])=[CH:17][N:18]=[C:13]2[C@@H:12]([CH2:49][C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:11]1)=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 2733832Lithium HexamethyldisilazideHCID 86587572HCID 86587572, compound

Product 1

HCID 86587571HCID 86587571, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 112a (101.6 mg, 0.205 mmol) in 1 mL THF at −78° C., was added 1N LiHMDS in THF (0.431 mL, 0.431 mmol). The mixture was stirred at −78° C. for 10 min, then t-butyl bromoacetate (30.3 μL, 0.205 mmol) was added, dropwise. The mixture was stirred at −78° C. for 5 h, then quenched with sat. NH4Cl. The mixture was diluted with EtOAc and washed with sat. NH4Cl and brine, dried (Na2SO4), and concentrated. The crude product was purified by flash chromatography to afford 110.7 mg (89%) of 112b. 1H NMR (300 MHz, CDCl3) δ9.38 (br s, 1H), 7.63 (br s, 1H), 7.45 (d, J=8.1, 2H), 7.33-7.17 (m, 12H), 7.02 (t, J=7.3, 1H), 5.17-5.11 (m, 3H), 4.84 (br s, 1H), 4.69 (br s, 1H), 3.62-3.51 (m, 1H), 2.84 (d, J=6.9, 2H), 2.79-2.67 (m, 1H), 2.40 (br s, 1H), 1.43 (s, 9H); MS (ESI) 609.2 (M+H+), 631.2 (M+Na+), 607.2 (M−H+).

Workup

  1. stirringThe mixture was stirred at −78° C. for 5 h
  2. customquenched with sat. NH4Cl
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with sat. NH4Cl and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-20bbdd58965e4b01bebf69141f3338a0
Source dataset
uspto-grants-2003_11
Patent number
US06653295B2

Reaction notes

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