Acetic Acid → (S)-4-(5-cyclopentylamino-2-fluoro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

HRID 1626111Notes

Reaction equation

HRID 1626111 reaction equation
[C:1]1(=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:7][C:8]1[CH:9]=[CH:10][C:11]([F:22])=[C:12]([C@:14]2([CH3:21])[CH2:19][CH2:18][O:17][C:16]([NH2:20])=[N:15]2)[CH:13]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH:1]1([NH:7][C:8]2[CH:9]=[CH:10][C:11]([F:22])=[C:12]([C@:14]3([CH3:21])[CH2:19][CH2:18][O:17][C:16]([NH2:20])=[N:15]3)[CH:13]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8452CyclopentanoneHCID 5049666Sodium triacetoxyborohydrideHCID 67236054(S)-4-(5-amino-2-fluoro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine

Product 1

HCID 71008825(S)-4-(5-cyclopentylamino-2-fluoro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamineYield 6.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of cyclopentanone (26.2 μl, 296 μmol) and (S)-4-(5-amino-2-fluoro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate A8.4) (60 mg, 269 μmol) in dichloromethane (2 ml) was treated with acetic acid (30.8 μl, 538 μmol) followed by sodium triacetoxyborohydride (85.4 mg, 403 μmol). The reaction mixture was stirred at room temperature for 2.5 hours. For the workup, the reaction mixture was quenched with a saturated solution of sodium hydrogencarbonate, then extracted with ethyl acetate. The organic layer was washed twice with water, dried over sodium sulphate, and evaporated at reduced pressure. The crude product was purified by chromatography on a silica-NH2 phase using a gradient of n-hexane/ethyl acetate=50:50 to 0:100 as the eluent to yield the (S)-4-(5-cyclopentylamino-2-fluoro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (5 mg, 6% yield). MS (ISP): m/z=292.1 [M+H]+.

Workup

  1. customFor the workup, the reaction mixture was quenched with a saturated solution of sodium hydrogencarbonate
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed twice with water
  4. dry with materialdried over sodium sulphate
  5. customevaporated at reduced pressure
  6. customThe crude product was purified by chromatography on a silica-NH2 phase

Sources & evidence

ORD record
ord-62cbbe50f82e4e3c9cb88c94b8355a3b
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

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