Bromochloromethane → HCID 86657995, compound

HRID 875257Notes

Reaction equation

HRID 875257 reaction equation
Br[CH2:2][Cl:3].C[O:5][C:6]([C@H:8]1[CH:13]=[CH:12][C:11]2[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:10]=2[O:9]1)=O.[Li]CCCC.CCCCCC>C1COCC1.O.C(O)(=O)C>[Cl:3][CH2:2][C:6]([C@H:8]1[CH:13]=[CH:12][C:11]2[CH:14]=[C:15]([F:18])[CH:16]=[CH:17][C:10]=2[O:9]1)=[O:5]

Participants

8

Reactant 4

HCID 6333BromochloromethaneHCID 8058HexaneHCID 67393369HCID 67393369, compoundHCID 178418339Butyllithium

Product 1

HCID 86657995HCID 86657995, compoundYield 101%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2.5 g of bromochloromethane (18.8 mmol) were added at room temperature to a solution of 2.0 g of (R)-6-Fluoro-1-benzopyran-2-carboxylic acid methyl ester, obtained after separation of the corresponding racemic mixture on a chiral chromatography column (9.4 mmol, 96.6% A, ee>99%), in 40 ml THF. The solution was then cooled to −80/−85° C. and 7.7 ml of 2.5 M n-BuLi in hexane (19 mmol) were slowly added to maintain the internal temperature between −75° C. and −80° C. The reaction progress was monitored by TLC. The solution was then acidified by the addition of 2 ml glacial acetic acid in 2 ml THF between −70° C. and −80° C. 10 ml of water were then added at −20/0° C. and the aqueous layer was then removed after decantation. The organic layer was concentrated under reduced pressure to give the title compound (2.2 g) as a white-off solid (ee: 97.2%, 94.8% A).

Workup

  1. customobtained
  2. customafter separation of the corresponding racemic mixture on a chiral chromatography column (9.4 mmol, 96.6% A, ee>99%)
  3. additionwere slowly added
  4. temperatureto maintain the internal temperature between −75° C. and −80° C
  5. customthe aqueous layer was then removed after decantation
  6. concentrationThe organic layer was concentrated under reduced pressure

Sources & evidence

ORD record
ord-a5ecc5c4d38d4c52aeef917ae0b16159
Source dataset
uspto-grants-2015_03
Patent number
US08981127B2

Reaction notes

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