1,2-Dichloroethane → HCID 117706273, compound

HRID 1778575Notes

Reaction equation

HRID 1778575 reaction equation
C(Cl)CCl.[C:5]1([CH2:17][N:18]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:19]2[CH2:23][CH2:22][C@@H:21]([C:24](O)=[O:25])[CH2:20]2)[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:7][CH:6]=1.Cl.[CH3:35][NH:36][O:37][CH3:38].C(N(CC)CC)C>CN(C1C=CN=CC=1)C.ClCCl.O>[C:30]([O:29][C:27](=[O:28])[N:18]([CH2:17][C:5]1[CH:6]=[CH:7][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:9][CH:10]=1)[C@H:19]1[CH2:23][CH2:22][C@@H:21]([C:24](=[O:25])[N:36]([O:37][CH3:38])[CH3:35])[CH2:20]1)([CH3:32])([CH3:33])[CH3:31]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 89527582HCID 89527582, compound

Product 1

HCID 117706273HCID 117706273, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

EDC (901 mg, 4.7 mmol) was added portion wise to a stirred solution of (1R,3S)-3-{(biphen-4-ylmethyl)-(tert-butoxycarbonyl)amino}-cyclopentane carboxylic acid (930 mg, 2.35 mmol), DMAP (10 mg), and N,O-dimethylhydroxylamine hydrochloride (459 mg, 4.7 mmol) in dichloromethane (15 mL). Triethylamine (1.31 mL, 9.4 mmol) was added drop wise, and the reaction mixture was stirred at room temperature overnight. The resulting solution was poured into water, 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, 10-60% ethyl acetate in heptane) gave tert-Butyl-biphen-4-ylmethyl-{(1S,3R)-3-(methoxy(methyl)carbamoyl)-cyclopentyl}-carbamate (800 mg, 78%) as a colorless oil; 1H NMR (CDCl3, 400 MHz) δ 7.61 (d, J=7.5 Hz, 2H), 7.54 (d, J=7.5 Hz, 2H), 7.45 (t, J=7.5 Hz, 2H), 7.35 (m, 1H), 7.30 (m, 2H), 4.72 (br, s, 1H), 4.49 (m, 2H), 3.68 (s, 3H), 3.19 (s, 3H), 3.10-3.20 (m, 1H), 2.10 (m, 1H), 1.64-2.01 (m, 5H), 1.41 (s, 9H).

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined organic phase was washed with saturated aqueous sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash column chromatography (silica gel, 10-60% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-ea92a1eed2dc49a7ba108be8b59830b9
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

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