Methyl 6-Bromohexanoate → HCID 22860743, compound

HRID 1956497Notes

Reaction equation

HRID 1956497 reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)[CH2:6][O:7][C@H:8]1[O:13][CH2:12][CH2:11][NH:10][C@@H:9]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Br[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][CH3:38])=[O:36]>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].CCOC(C)=O>[F:28][C:2]([F:1])([F:27])[C:3]1[CH:4]=[C:5]([CH:20]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:22]=1)[CH2:6][O:7][C@H:8]1[O:13][CH2:12][CH2:11][N:10]([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][CH3:38])=[O:36])[C@@H:9]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 2

HCID 4170292Methyl 6-BromohexanoateHCID 10811257HCID 10811257, compound

Product 1

HCID 22860743HCID 22860743, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 0.259 g (0.64 mmol) of 2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenylmorpholine (from example 33) in 2 mL of DMF were added 0.16 g (0.77 mmol) of methyl 6-bromohexanoate, 0.155 g (1.12 nmmol) of K2C03 and 2 crystals of nBu4NI. The resulting solution was heated in a 60° C. bath for 36 h, at which time a tlc indicated incomplete reaction. The bath temperature was raised to 100° C. After 3 h the reaction mixture was cooled and diluted with EtOAc. The EtOAc solution was washed with water (2×), brine and dried over Na2SO4. The filtrate was concentrated and the residue was chromatographed using 30% EtOAc/hexane to isolate 220 mg (65%) of the product. 1H-NMR (400 MHz, CDCl3): δ 1.0-1.4 (m, 4 H), 1.47 (m, J=8 Hz, 2H), 1.95 (m, 1H), 2.2 (t, J=8 Hz, 2H), 2.35 (m, 2H), 2.9 (d, J=13 Hz, 1H), 3.07 (d, J=7 Hz, 1H), 3.62 (s, 3H), 3.81 (td, J=8 Hz and 2 Hz, 1 H), 4.04 (dd, J=10 Hz and 2 Hz, 1H), 4.36 (d, J=7 Hz, 1H), 4.4 (d, J=13 Hz, 1H), 4.79 (d, J=13 Hz, 1H), 7.2-7.4 (m, 7H), 7.66 (s, 1H).

Workup

  1. customreaction
  2. temperatureThe bath temperature was raised to 100° C
  3. temperatureAfter 3 h the reaction mixture was cooled
  4. washThe EtOAc solution was washed with water (2×), brine
  5. dry with materialdried over Na2SO4
  6. concentrationThe filtrate was concentrated
  7. customthe residue was chromatographed

Sources & evidence

ORD record
ord-7867b9ab89fb45ba952eaee545a5c84d
Source dataset
uspto-grants-1998_07
Patent number
US05780467

Reaction notes

Loading…