1,2-Dichloroethane → Tert-butyl{(cis)-2-[(2,2,2-trifluoroethyl)carbamoyl]cyclohexyl}carbamate

HRID 510182Notes

Reaction equation

HRID 510182 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:18][C:19]([F:23])([F:22])[CH2:20][NH2:21].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C(Cl)CCl>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]1[C:15](=[O:17])[NH:21][CH2:20][C:19]([F:23])([F:22])[F:18])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 9773Ethanamine, 2,2,2-trifluoro-HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1512487cis-2-((tert-Butoxycarbonyl)amino)cyclohexanecarboxylic acid

Product 1

HCID 97027465Tert-butyl{(cis)-2-[(2,2,2-trifluoroethyl)carbamoyl]cyclohexyl}carbamateYield 95.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of cis-2-tertbutoxycarbonylamino-cyclohexanecarboxylic acid (Acros, 2 g, 8.22 mmol), 2,2,2-trifluoroethylamine (0.969 mL, 12.33 mmol), HOBT (1.888 g, 12.33 mmol) and DIPEA (4.31 mL, 24.66 mmol) in DMF (10 mL) was added EDC (2.364 g, 12.33 mmol) and the mixture allowed to stir at RT for 1 hr. The reaction was quenched into 10% aq. KHSO4 (100 mL) and product extracted with ethyl acetate (100 mL). Organic washed with aq. NaHCO3 (50 mL) and then brine (50 mL). Aqueous extracts backwashed with ethyl acetate (50 mL) and organic extracts combined, dried over sodium sulfate, filtered and concentrated to give 2.55 gm of a white solid, I-5a. 1H NMR (600 MHz, CDCl3) δ 6.18 (m, 1H), 5.07 (m, 1H), 3.75-4.0 (m 3H), 2.62 (m, 1H), 1.3-2.0 (br m, 8H), 1.40 (s, 9H).

Workup

  1. customThe reaction was quenched into 10% aq. KHSO4 (100 mL) and product
  2. extractionextracted with ethyl acetate (100 mL)
  3. washOrganic washed with aq. NaHCO3 (50 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-92f9af80388e4d9199547d75750b5cfe
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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