Dichloromethane → (1S,2S)-1-acetamido-N-tert-butyl-2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)cyclopentanecarboxamide

HRID 61347

Reaction equation

HRID 61347 reaction equation
[C:1]([NH:4][C@@:5]1([C:13]([NH:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8][CH2:7][C@@H:6]1[CH2:10][CH:11]=[CH2:12])(=[O:3])[CH3:2].C(Cl)Cl.[CH3:23][C:24]1([CH3:31])[C:28]([CH3:30])([CH3:29])[O:27][BH:26][O:25]1>C1C=CC(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[C:1]([NH:4][C@@:5]1([C:13]([NH:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8][CH2:7][C@@H:6]1[CH2:10][CH2:11][CH2:12][B:26]1[O:27][C:28]([CH3:30])([CH3:29])[C:24]([CH3:31])([CH3:23])[O:25]1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 69669622(1S,2R)-1-acetamido-2-allyl-N-tert-butylcyclopentanecarboxamide

Product 1

HCID 69669489(1S,2S)-1-acetamido-N-tert-butyl-2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)cyclopentanecarboxamideYield 78.3%

Reagents, catalysts & solvents 2

HCID 742671,2-Bis(diphenylphosphino)ethaneCatalystHCID 962WaterSolvent

Procedure

A stirred solution of (1S,2R)-1-acetamido-2-allyl-N-tert-butylcyclopentanecarboxamide (0.599 g, 2.25 mmol) in an anhydrous methylene chloride (9 mL) under nitrogen was treated with Ir2Cl2(COD)2 (45 mg, 0.07 mmol) and DiPhos (54 mg, 0.136 mmol) and stirred at room temperature for 30 min. 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.65 mL, 4.48 mmol) was added dropwise and the solution stirred at room temperature for 20 h. The reaction mixture was poured into water (20 mL) and extracted with ethyl acetate (40 mL, then 2×15 mL), and the combined organic solution was washed with saturate aqueous sodium chloride (30 mL), dried over MgSO4, and concentrated. The residue was dissolved in minimal dichloromethane and purified by flash column chromatography (silica gel, 40-50% ethyl acetate in heptane) to afford (1S,2S)-1-acetamido-N-tert-butyl-2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl) cyclopentanecarboxamide (0.695 g, 78%) as a white solid. 1H NMR (CDCl3, 300 MHz) δ 6.72 (br s, NH, 1 H), 5.68 (br s, NH, 1 H), 2.46-2.29 (m, 2 H), 2.10-2.19 (m, 1 H), 2.02 (s, 3 H), 2.00-1.88 (m, 1 H), 1.75-1.60 (m, 3 H), 1.52-1.38 (4 H), 1.32 (s, 9 H), 1.31 (s, 12 H), 0.81-0.70 (m, 2 H); MS (+CI): m/z for C21H39BN2O4: expected 394.3; found 395.2 (M+H)+.

Workup

  1. stirringthe solution stirred at room temperature for 20 h
  2. extractionextracted with ethyl acetate (40 mL
  3. wash2×15 mL), and the combined organic solution was washed with saturate aqueous sodium chloride (30 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in minimal dichloromethane
  7. custompurified by flash column chromatography (silica gel, 40-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-46d8db09e1b0440c98cacf2ddefd7b4b
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Linked notes

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