2,2,2-Trifluoroethanol → HCID 68467883, compound

HRID 218063Notes

Reaction equation

HRID 218063 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[CH:10]([CH2:11][CH:12]([C:16]([OH:18])=[O:17])[CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:19][C:20]([F:24])([F:23])[CH2:21]O.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]2[CH:14]([CH2:13][CH:12]([C:16]([O:18][CH2:21][C:20]([F:24])([F:23])[F:19])=[O:17])[CH2:11]2)[CH2:15]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 10868Dicyclohexylcarbodiimide2×HCID 438109002-(tert-Butoxycarbonyl)octahydrocyclopenta[c]pyrrole-5-carboxylic acid

Product 1

HCID 68467883HCID 68467883, compoundYield 27%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]octane-7-carboxylic acid (0.150 g, 0.588 mmol), 2,2,2-trifluoroethanol (0.118 g, 1.18 mmol), 4-N,N-dimethylaminopyridine (DMAP) (0.143 g, 1.18 mmol) and polymer supported dicyclohexylcarbodiimide (PS-DCC) (0.8 g, loading 3.2 mmol/g) in dichloromethane (20 mL) was stirred at ambient temperature overnight. The reaction mixture was filtered, and the filtrate was concentrated. The residue was purified by HPLC, using acetonitrile and 0.05% aqueous TFA as mobile phase, to obtain 0.053 g (27% yield) of 2,2,2-trifluoroethyl 3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]octane-7-carboxylate as an oil (1H NMR (CDCl3, 300 MHz): δ 4.48 (q, J=8.30 Hz, 2H), 3.58-3.46 (m, 2H), 3.26-2.92 (m, 4H), 2.82-2.63 (m, 1H), 2.28-2.07 (m, 2H, 1.84-1.65 (m, 2H), 1.45 (s, 9H); MS (m/z): 338 (M+1), 282 (M+1-56)). The 2,2,2-trifluoroethyl 3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]octane-7-carboxylate was dissolved in dichloromethane (5.0 mL), treated with TFA (2.0 mL), and the reaction was stirred at ambient temperature for 1 h. The solvent was evaporated and the crude product was purified on HPLC, using acetonitrile and 0.05% TFA in water as mobile phase, to obtain 0.023 g of the trifluoroacetate salt of 2,2,2-trifluoroethyl 3-azabicyclo[3.3.0]octane-7-carboxylate (as a cis/trans mixture) as an oil (1H NMR (CD3OD, 300 MHz): δ 4.62 (q, J=8.79 Hz, 2H), 3.64-3.42 (m, 1H), 3.3.38-3.32 (m, 1H), 3.22-3.05 (m, 2H), 3.02-2.95 (m, 3H), 2.42-2.07 (m, 2H), 1.96-1.63 (m, 2H); MS (m/z): 238 (M+1)).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated
  3. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-71daabafff1648c1911448bbaef8dbee
Source dataset
uspto-grants-2012_06
Patent number
US08198296B2

Reaction notes

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