Trifluoroacetic acid → Benzyl (3R)-6-(2,3-difluorophenyl)-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-ylcarbamate

HRID 20131

Reaction equation

HRID 20131 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[C:16]1[CH2:22][N:21](CC2C=CC(OC)=CC=2OC)[C:20](=[O:34])[C@H:19]([NH:35][C:36](=[O:45])[O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:18][CH:17]=1>ClCCl>[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[C:16]1[CH2:22][NH:21][C:20](=[O:34])[C@H:19]([NH:35][C:36](=[O:45])[O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:18][CH:17]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86595036Benzyl (3R)-6-(2,3-difluorophenyl)-1-(2,4-dimethoxybenzyl)-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-ylcarbamate

Product 1

HCID 86595037Benzyl (3R)-6-(2,3-difluorophenyl)-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-ylcarbamateYield 66.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (60 mL) was added to a solution of benzyl (3R)-6-(2,3-difluorophenyl)-1-(2,4-dimethoxybenzyl)-2-oxo-2,3,4,7-tetrahydro-1H-azepin-3-ylcarbamate (3.70 g, 7.08 mmol) in dichloromethane (40 mL). After 18 h, the mixture was concentrated at 25° C., methanol (150 mL) was added, and the precipitate filtered. The filtrate was concentrated, diluted with dichloromethane (100 mL), washed with water (2×), saturated aqueous sodium bicarbonate (2×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (5% ethyl acetate/hexanes→65% ethyl acetate/hexanes) gave the title compound (1.75 g). MS 373.1 (M+1).

Workup

  1. concentrationthe mixture was concentrated at 25° C.
  2. additionmethanol (150 mL) was added
  3. filtrationthe precipitate filtered
  4. concentrationThe filtrate was concentrated
  5. additiondiluted with dichloromethane (100 mL)
  6. washwashed with water (2×), saturated aqueous sodium bicarbonate (2×), saturated brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by silica gel chromatography (5% ethyl acetate/hexanes→65% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-324237fd2ebd43c7ba15a87be4adfd47
Source dataset
uspto-grants-2010_06
Patent number
US07745427B2

Linked notes

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