Water → HCID 68584487, compound

HRID 733090Notes

Reaction equation

I[CH2:2][C:3]1([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5][CH2:4]1.[C:13]([O:17][C:18](=[O:27])[NH:19][CH2:20][CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)([CH3:16])([CH3:15])[CH3:14].C(N(CC)C(C)C)(C)C.O>CN(C)C=O>[C:13]([O:17][C:18]([NH:19][CH2:20][CH:21]1[CH2:22][CH2:23][N:24]([CH2:2][C:3]2([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5][CH2:4]2)[CH2:25][CH2:26]1)=[O:27])([CH3:16])([CH3:14])[CH3:15]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of tert-butyl 1-(iodomethyl)cyclopropanecarboxylate (1.9 g 6.7 mmol, step 1 of Example 3), tert-butyl(piperidin-4-ylmethyl)carbamate (3.0 g, 14 mmol), N,N-diisopropylethylamine (5.8 mL, 34 mmol) in N,N-dimethylformamide (25 mL) was heated at 120° C. for 20 h. After cooled to room temperature, water (50 mL) was added, extracted with ethyl acetate/toluene (1:2, 60 mL×2), washed with water (50 mL×2), brine (50 mL), dried over MgSO4, filtered and concentrated to give brown oil. The oil was chromatographed on a column of silica gel eluting with CH2Cl2/methanol (10:1) to give 560 mg (1%) of the title compound as clear brown oil. MS (ESI) m/z: 369 (M+H)+. 1H-NMR (CDCl3) δ: 4.60 (1H, br), 3.08-2.82 (4H, m), 2.59 (2H, s), 2.10-1.90 (2H, m), 1.75-1.55 (4H, m), 1.50-1.05 (23H, m).

Workup

temperatureAfter cooled to room temperature
extractionextracted with ethyl acetate/toluene (1:2, 60 mL×2)
washwashed with water (50 mL×2), brine (50 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customto give brown oil
customThe oil was chromatographed on a column of silica gel eluting with CH2Cl2/methanol (10:1)

Sources & evidence

ORD record: ord-bdcd437d58fc4578985b5e5c49c73749
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07589109B2

Reaction notes

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