1-Benzyloxy-4-bromo-2,5-difluorobenzene → HCID 67073314, compound

HRID 2253031Notes

Reaction equation

HRID 2253031 reaction equation
C([Mg]Br)(C)C.C([Li])CCC.[CH2:11]([O:18][C:19]1[CH:24]=[C:23]([F:25])[C:22](Br)=[CH:21][C:20]=1[F:27])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][O:38][C@H:37]([C:41](=[O:46])N(OC)C)[CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>O1CCCC1.O>[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][O:38][C@H:37]([C:41](=[O:46])[C:22]2[CH:21]=[C:20]([F:27])[C:19]([O:18][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:24][C:23]=2[F:25])[CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]

Participants

7

Reactant 4

HCID 580861601-Benzyloxy-4-bromo-2,5-difluorobenzeneHCID 591669901,1-Dimethylethyl (2S)-2-[(methoxymethylamino)carbonyl]-4-morpholinecarboxylateHCID 178418339ButyllithiumHCID 178418365HCID 178418365, compound

Product 1

HCID 67073314HCID 67073314, compoundYield 64.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 33 mL of isopropylmagnesium bromide (1M in tetrahydrofuran) in tetrahydrofuran (120 mL) was added with cooling (max+3° C.) n-butyllithium (41 mL, 1.6M in hexane). The mixture was cooled to −78° C., 1-benzyloxy-4-bromo-2,5-difluoro-benzene (8.2 g, 27 mmol) was added and stirred for 1.5 hours at this temperature. (S)-2-(Methoxy-methyl-carbamoyl)-morpholine-4-carboxylic acid tert-butyl ester (7.5 g, 27 mmol) was added dropwise within 10 min at −75° C. Stirring at −78° C. continued for 1 h and the reaction mixture was than poured into water (600 mL). Organic material was partitioned into ethyl acetate (3×), organic phases were pooled, washed with brine and dried with MgSO4 before being concentrated in vacuo. The residue was then purified by column chromatography (heptane-ethyl acetate (2:1)/silica gel) to give 7.5 g of the title compound.

Workup

  1. stirringStirring at −78° C.
  2. waitcontinued for 1 h
  3. customOrganic material was partitioned into ethyl acetate (3×), organic phases
  4. washwashed with brine
  5. dry with materialdried with MgSO4
  6. concentrationbefore being concentrated in vacuo
  7. customThe residue was then purified by column chromatography (heptane-ethyl acetate (2:1)/silica gel)

Sources & evidence

ORD record
ord-2615c4f640964a19874a8b1b316b22b1
Source dataset
uspto-grants-2008_01
Patent number
US07323466B2

Reaction notes

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