Sodium hydride → HCID 118096920, compound

HRID 2171287Notes

Reaction equation

HRID 2171287 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:20]([C:21]([OH:23])=[O:22])[CH2:19][C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[F:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Br)=[CH:29][CH:28]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[C@H:20]([C:21]([OH:23])=[O:22])[CH2:19][C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:31][C:30]3[CH:33]=[CH:34][C:27]([F:26])=[CH:28][CH:29]=3)[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 680214-Fluorobenzyl bromideHCID 1268155BOC-L-1,2,3,4-TETRAHYDRONORHARMAN-3-CARBOXYLIC ACID

Product 1

HCID 118096920HCID 118096920, compoundYield 72.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The acid 2 (20.0 g, 63.2 mmol) in DMF (630 mL) was degassed and the flask was cooled in ice water bath. NaH (60% in mineral oil; 7.8 g, 196.0 mmol) was slowly added portionwise over 45 min at 0° C. and stirred for 1 hr. 4-fluorobenzyl bromide (8.7 mL, 69.5 mmol) was added dropwise over 45 min at 0° C. and stirred for 1.5 hr. The reaction quenched with water. The mixture diluted with water (1.8 L) and washed with EtOAc (1 L). The aqueous layer was acidified to pH 3-4 with solid citric acid. The mixture extracted with EtOAc (3×300 mL). The combined organic extracts were washed with water (900 mL), brine (200 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified by silica gel column chromatography using 0-30% EtOAc/Hexane to give a solid. The solid was washed with 10% CH2Cl2/hexane to afford the acid 3 (19.5 g, 72%) as a white powder. 1H NMR (300 MHz, DMSO-d6): δ 12.81 (br s, 1H), 7.48-7.42 (m, 2H), 7.13-6.97 (m, 6H), 5.41-5.28 (m, 2H), 5.14-5.03 (m, 1H), 4.66-4.58 (m, 1H), 4.42-4.27 (m, 1H), 3.32-3.28 (m, 1H), 3.06-2.96 (m, 1H), 1.40 (s, 9×½H), 1.39 (s, 9×½H); LC-MS [M+H+ 425].

Workup

  1. stirringstirred for 1.5 hr
  2. customThe reaction quenched with water
  3. additionThe mixture diluted with water (1.8 L)
  4. washwashed with EtOAc (1 L)
  5. extractionThe mixture extracted with EtOAc (3×300 mL)
  6. washThe combined organic extracts were washed with water (900 mL), brine (200 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude was purified by silica gel column chromatography
  11. customto give a solid
  12. washThe solid was washed with 10% CH2Cl2/hexane

Sources & evidence

ORD record
ord-df5fbb1a872a44f2bc0ac5d20bd2a81b
Source dataset
uspto-grants-2015_06
Patent number
US09051320B1

Reaction notes

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