Ethyldiphenylphosphine → N-(3-(2-acetamido-1-(tert-butylamino)-1-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-2-yl)-1-(4-chlorophenyl)cyclobutyl)benzamide

HRID 1778594Notes

Reaction equation

HRID 1778594 reaction equation
C1(P(CC)C2C=CC=CC=2)C=CC=CC=1.[CH3:16][C:17]1([CH3:24])[C:21]([CH3:23])([CH3:22])[O:20][BH:19][O:18]1.[C:25]([NH:28][C:29]([CH:41]1[CH2:44][C:43]([NH:52][C:53](=[O:60])[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)([C:45]2[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][CH:46]=2)[CH2:42]1)([CH2:37][CH2:38][CH:39]=[CH2:40])[C:30]([NH:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])(=[O:27])[CH3:26]>ClCCl>[C:25]([NH:28][C:29]([CH:41]1[CH2:44][C:43]([NH:52][C:53](=[O:60])[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)([C:45]2[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][CH:46]=2)[CH2:42]1)([CH2:37][CH2:38][CH2:39][CH2:40][B:19]1[O:20][C:21]([CH3:23])([CH3:22])[C:17]([CH3:24])([CH3:16])[O:18]1)[C:30]([NH:32][C:33]([CH3:36])([CH3:34])[CH3:35])=[O:31])(=[O:27])[CH3:26]

Participants

5

Reactant 3

HCID 69082EthyldiphenylphosphineHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 89514269N-(3-(2-acetamido-1-(tert-butylamino)-1-oxohex-5-en-2-yl)-1-(4-chlorophenyl)cyclobutyl)benzamide

Product 1

HCID 89515342N-(3-(2-acetamido-1-(tert-butylamino)-1-oxo-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexan-2-yl)-1-(4-chlorophenyl)cyclobutyl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

While under argon, a solution of bis(1,5-dicyclooctadiene)diiridium(I)dichloride (58 mg, 0.086 mmol) and diphenylphosphinoethane (68 mg, 0.172 mmol) in dichloromethane (10 mL) was cooled to 0° C., and charged with 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.66 mL, 11.44 mmol). After stirring for 15 min, a solution of N-(3-(2-acetamido-1-(tert-butylamino)-1-oxohex-5-en-2-yl)-1-(4-chlorophenyl)cyclobutyl)benzamide (1.46 g, −2.8 mmol) in dichloromethane (35 mL) was added in one portion and the resulting solution was allowed to slowly warm to room temperature. After stirring for 16 h dichloromethane (40 mL) added and the organic layer was washed with water and saturated aqueous sodium chloride. The resulting solution was dried over MgSO4, filtered and concentrated to give the crude product as a mixture of diastereomers. Purification by flash column chromatography (20-80% ethyl acetate in heptane) gave two products. The more lipophilic isomer was isolated and used in the next step (590 mg, 0.924 mmol). 1H NMR (CDCl3, 600 MHz) δ 8.65 (s, 1H), 7.97 (s, 1H), 7.67 (d, J=7.2 Hz, 2H), 7.49-7.53 (m, 3H), 7.40-7.43 (m, 4H), 6.17 (s, 1H), 3.37-3.42 (m, 1H), 3.30-3.34 (m, 1H), 2.72-2.80 (m, 2H), 2.39-2.51 (m, 2H), 2.31 (s, 3), 1.66-1.72 (m, 2H), 1.30 (s, 9H), 1.19 (s, 12H), 1.10-1.17 (m, 2H), 0.83-8.89 (m, 1H), 0.72 (t, J=7.8 Hz, 2H). ESI MS found for C35H49BClN3O5 m/z [638.7/640.8 (M+1), 636.7/638.9 (M−1)]

Workup

  1. additionadded
  2. washthe organic layer was washed with water and saturated aqueous sodium chloride
  3. dry with materialThe resulting solution was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-688e07c4a5434f648a65344b866ce93b
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

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