Dicyclohexylcarbodiimide → HCID 58993644, compound

HRID 391423Notes

Reaction equation

HRID 391423 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:14]([OH:16])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(N=C=NC2CCCCC2)CCCCC1.[Br:38][C:39]1[CH:40]=[C:41]([C@H:49](O)[CH3:50])[CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1.CN(C1C=CC=CN=1)C>C1(C)C=CC=CC=1.ClCCl>[C:17]1([C:11]2([C:14]([O:16][C@@H:49]([C:41]3[CH:42]=[C:43]([C:45]([F:46])([F:47])[F:48])[CH:44]=[C:39]([Br:38])[CH:40]=3)[CH3:50])=[O:15])[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 218852-DimethylaminopyridineHCID 7369171-((Tert-butoxy)carbonyl)-4-phenylpiperidine-4-carboxylic acidHCID 58993662HCID 58993662, compound

Product 1

HCID 58993644HCID 58993644, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 1-(tert-butoxycarbonyl)-4-phenylpiperidine-4-carboxylic acid (3.8 g, 10.3 mmol) in a dichloromethane (5 mL) and toluene (30 mL) mixture was treated with 1,3-dicyclohexylcarbodiimide (2.96 g, 14.4 mmol) and stirred for 30 min. The suspension was cooled to 0° C. and treated with (R)-1-(3-bromo-5-(trifluoromethyl)phenyl)ethanol (2.79 g, 10.3 mmol) and dimethylaminopyridine (1.26 g, 10.3 mmol). The ice bath was removed and the suspension stirred at room temperature for 60 h. The reaction mixture was poured into pentane, filtered, and the solids washed several times with pentane. The filtrate was washed with 1 N hydrochloric acid (1×), water (2×), then 1 N sodium hydroxide, then brine (2×), dried over sodium sulfate, and concentrated. Flash chromatography on silica gel (12% ethyl acetate/hexanes) gave 4.8 g (84%) as a light yellow oil. 1H NMR (500 MHz, CDCl3) δ ppm 7.58 (s, 1H), 7.23-7.33 (m, 6H), 7.19 (s, 1H), 5.80 (q, J=6.6 Hz, 1H), 3.82-3.97 (m, 2H), 2.97-3.09 (m, 2H), 2.44-2.53 (m, 2H), 1.76-2.01 (m, 2H), 1.42 (s, 9H), 1.40 (m, 3H). Mass spec.: 558.06 (MH)+.

Workup

  1. customThe ice bath was removed
  2. stirringthe suspension stirred at room temperature for 60 h
  3. additionThe reaction mixture was poured into pentane
  4. filtrationfiltered
  5. washthe solids washed several times with pentane
  6. washThe filtrate was washed with 1 N hydrochloric acid (1×), water (2×)
  7. dry with material1 N sodium hydroxide, then brine (2×), dried over sodium sulfate
  8. concentrationconcentrated
  9. customFlash chromatography on silica gel (12% ethyl acetate/hexanes) gave 4.8 g (84%) as a light yellow oil

Sources & evidence

ORD record
ord-30b3f53aca7542d7a01b68c4b691d1bc
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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