Methyl bromoacetate → HCID 9934727, compound

HRID 1956486Notes

Reaction equation

HRID 1956486 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)[CH2:6][O:7][CH:8]1[O:13][CH2:12][CH2:11][NH:10][CH:9]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)C(C)C)(C)C.Br[CH2:39][C:40]([O:42][CH3:43])=[O:41]>C(#N)C>[F:28][C:2]([F:1])([F:27])[C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:22]=1)[CH2:6][O:7][CH:8]1[O:13][CH2:12][CH2:11][N:10]([CH2:39][C:40]([O:42][CH3:43])=[O:41])[CH:9]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 9801388HCID 9801388, compound

Product 1

HCID 9934727HCID 9934727, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 150 mg (0.37 mmol) of the trans-isomer of (+/-)-2-(3,5-bis(trifluoromethyl)benzyloxy)-3-phenyl morpholine (Example 4) and 0.18 mL (1.00 mmol) of N,N-diisopropyl-ethyl- amine in 2 mL of acetonitrile was treated with 0.095 mL (1.00 mmol) of methyl bromoacetate and the resulting solution was stirred at rt for 20 h. The solution was concentrated in vacuo and the residue was partitioned between 20 mL of ethyl acetate and 5 mL of 0.5N aqueous potassium hydrogen sulfate solution. The layers were separated; the organic layer was washed with 10 mL of saturated aqueous sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo. Flash chromatography on 10 g of silica gel using 4:1 v/v hexanes/ether as the eluant afforded 164 mg (93%) of the trans-isomer of the title compound as an oil: 1H NMR 2.79 (dt, 1 H, J=3.2, 11.2), 2.93 (dt, 1 H, J=11.2, 1.6), 3.52 (d, 1 H, J=7.2), 3.63 (s, 3 H), 3.92 (dt, 1 H, J=2.8, 11.6), 4.04 (ddd, 1 H, J=11.6, 3.2, 1.6), 4.45 and 4.84 (AB q, 2 H, J=13.2), 4.46 (d, 1 H, J=7.2), 7.31 - 7.38 (m, 6 H), 7.68 (s, 1 H); IR (neat) 2861, 1744, 1455, 1375, 1346, 1278, 1170, 887, 759, 704, 682; FAB-MS 478(M+1)+. Analysis Calcd for C22H21F6NO4 : C, 55.35; H, 4.43; N, 2.93; F, 23.88. Found: C, 55.74; H, 4.50; N, 2.79; F, 24.01.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. customthe residue was partitioned between 20 mL of ethyl acetate and 5 mL of 0.5N aqueous potassium hydrogen sulfate solution
  3. customThe layers were separated
  4. washthe organic layer was washed with 10 mL of saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ead563b3167c47d88cb62b5795b40993
Source dataset
uspto-grants-1998_07
Patent number
US05780467

Reaction notes

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