Bromide ion → HCID 89526867, compound

HRID 1778576Notes

Reaction equation

HRID 1778576 reaction equation
[C:1]([O:5][C:6](=[O:32])[N:7]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:22][CH:21]=1)[C@H:8]1[CH2:12][CH2:11][C@@H:10]([C:13](=[O:18])N(OC)C)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Br-].O.Cl>O1CCCC1>[C:1]([O:5][C:6](=[O:32])[N:7]([CH2:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:24][CH:25]=1)[C@H:8]1[CH2:12][CH2:11][C@@H:10]([C:13](=[O:18])[CH2:10][CH2:9][CH:8]=[CH2:12])[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 259Bromide ionHCID 313Hydrochloric AcidHCID 962WaterHCID 117706273HCID 117706273, compound

Product 1

HCID 89526867HCID 89526867, compoundYield 188.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

While under a nitrogen atmosphere, a solution of tert-Butyl-biphen-4-ylmethyl-{(1S,3R)-3-(methoxy(methyl)carbamoyl)-cyclopentyl}-carbamate (1.2 g, 2.74 mmol), in tetrahydrofuran (20 mL) was cooled to 0° C. and treated with 3-butenylmagnesiun bromide (0.5 M in THF, 13.7 mL, 6.85 mmol) in a drop wise manner. The solution was stirred for 1 hour at 0° C. then allowed to warm to room temperature overnight. The resulting solution was poured into water, acidified to pH 3-4 with 1 N hydrochloric acid, and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (silica gel, 0-30% ethyl acetate in heptane) gave tert-Butyl-biphen-4-ylmethyl-{(1S,3R)-3-pent-4-enoylcyclopentyl}-carbamate as a colorless oil (1.12 g, 94%); 1H NMR (CDCl3, 400 MHz) δ 7.62 d, J=7.5 Hz, (2H), 7.56 (d, J=7.5 Hz, 2H), 7.46 (t, J=7.5 Hz, 2H), 7.36 (m, 1H), 7.28 (m, 2H), 5.80 (m, 1H), 5.01 (m, 2H), 4.48 m, (3H), 2.92 (m, 1H), 2.54 (m, 2H), 2.37 (m, 2H), 2.04 (m, 1H), 1.74-1.94 (m, 4H), 1.48-1.66 (m, 1H), 1.43 (s, 9H).

Workup

  1. temperatureto warm to room temperature overnight
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic phase was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography (silica gel, 0-30% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-ffe81460160f46f6960fb93cdb3b682d
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

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