Trifluoroacetic acid → Phenylmethyl [(2R,4S)-2-(4-fluoro-2-methylphenyl)-4-(2-propen-1-yl)-4-piperidinyl]carbamate

HRID 384021Notes

Reaction equation

HRID 384021 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][C@:12]([NH:17][C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])([CH2:14][CH:15]=[CH2:16])[CH2:11][CH2:10][N:9]2C(OC(C)(C)C)=O)=[C:4]([CH3:35])[CH:3]=1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>ClCCl>[C:22]1([CH2:21][O:20][C:18](=[O:19])[NH:17][C@@:12]2([CH2:14][CH:15]=[CH2:16])[CH2:11][CH2:10][NH:9][C@@H:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=3[CH3:35])[CH2:13]2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 581699221,1-dimethylethyl (2R,4S)-2-(4-fluoro-2-methylphenyl)-4-({[(phenylmethyl)oxy]carbonyl}amino)-4-(2-propen-1-yl)-1-piperidinecarboxylate2×

Product 1

HCID 58169883Phenylmethyl [(2R,4S)-2-(4-fluoro-2-methylphenyl)-4-(2-propen-1-yl)-4-piperidinyl]carbamateYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1,1-dimethylethyl (2R,4S)-2-(4-fluoro-2-methylphenyl)-4-({[(phenylmethyl)oxy]carbonyl}amino)-4-(2-propen-1-yl)-1-piperidinecarboxylate (Intermediate 17 29 g, 60.1 mmol) in dry Dichloromethane (DCM) (500 ml), at 0° C., TFA (125 ml, 1622 mmol) was slowly added in 30 mins and the reaction mixture was stirred for 2 hours at the same temperature. The reaction was diluted with DCM (300 ml) and a saturated solution of NaHCO3 was added until pH=8. Two phases were separated and the aqueous layer was extracted with DCM (200 ml). Combined organic layers were dried (Na2SO4), filtered and evaporated affording the title compound (23.0 g, 60.1 mmol, quantitative yield) as a colourless oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.46-7.56 (m, 1H) 7.25-7.41 (m, 5H) 7.07 (br. s., 1H) 6.92-7.03 (m, 2H) 5.67-5.83 (m, 1H) 5.03-5.19 (m, 2H) 4.97 (s, 2H) 3.96 (d, 1H) 2.82-3.03 (m, 2H) 2.76 (d, 2H) 2.29 (s, 3H) 1.99 (d, 2H) 1.54-1.68 (m, 1H) 1.36 (t, 1H); UPLC: Rt=0.62 mins, m/z=383 [M+H].

Workup

  1. customTwo phases were separated
  2. extractionthe aqueous layer was extracted with DCM (200 ml)
  3. dry with materialCombined organic layers were dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-80e0198ad189429f92c6dfd906ddda91
Source dataset
uspto-grants-2013_02
Patent number
US08367692B2

Reaction notes

Loading…