(4R)-2-Hydroxy-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinan 2-oxide → (-)-(cis)-7-bromo-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepine-1-amine (4S)-2-hydroxy-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinane 2-oxide

HRID 1668358Notes

Reaction equation

HRID 1668358 reaction equation
[Br:1][C:2]1[C:22]([F:23])=[CH:21][C:5]2[O:6][C:7]3[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:8]=3[C@H:9]3[C@H:14]([NH2:15])[CH2:13][CH2:12][CH2:11][N:10]3[C:4]=2[CH:3]=1.[CH3:24][C:25]1([CH3:39])[C@@H:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:30][P:28]([OH:38])(=[O:29])[O:27][CH2:26]1>C(Cl)Cl.CC(O)C.C(O)C>[OH:38][P:28]1(=[O:29])[O:30][C@@H:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:25]([CH3:24])([CH3:39])[CH2:26][O:27]1.[Br:1][C:2]1[C:22]([F:23])=[CH:21][C:5]2[O:6][C:7]3[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:8]=3[C@H:9]3[C@H:14]([NH2:15])[CH2:13][CH2:12][CH2:11][N:10]3[C:4]=2[CH:3]=1

Participants

6

Reactant 2

HCID 9829482(4R)-2-Hydroxy-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinan 2-oxideHCID 67359100(-)-(cis)-7-bromo-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepine-1-amine

Product 1

HCID 67360179(-)-(cis)-7-bromo-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepine-1-amine (4S)-2-hydroxy-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinane 2-oxideYield 39.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 3776IsopropanolSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
40 °C

Procedure

To a solution of (±)-(cis)-7-bromo-8,12-difluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepine-1-amine (12.06 g, 31.65 mmol) in 120 mL of CH2Cl2, 25 mL of 2-propanol and 25 mL of ethanol at 40° C. was added a warm solution of (+)-phencyphos (3.84 g, 15.82 mmol) in 50 mL of CH2Cl2, 25 mL of 2-propanol and 25 mL of ethanol. The mixture was heated at 40° C., CH2Cl2 was carefully evaporated until a small amount of crystals was formed, and then the mixture was gradually cooled down to ambient temperature. The precipitate was filtered off and recrystallized to yield the title compound (3.94 g, 20%).

Workup

  1. customCH2Cl2 was carefully evaporated until a small amount of crystals
  2. customwas formed
  3. temperaturethe mixture was gradually cooled down to ambient temperature
  4. filtrationThe precipitate was filtered off
  5. customrecrystallized

Sources & evidence

ORD record
ord-64a465aed06e4e23a105ee6836ba091a
Source dataset
uspto-grants-2011_08
Patent number
US07989442B2

Reaction notes

Loading…