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

HRID 1668349Notes

Reaction equation

HRID 1668349 reaction equation
[Br:1][C:2]1[C:21]([F:22])=[CH:20][C:5]2[O:6][C:7]3[CH:19]=[CH:18][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.[CH3:23][C:24]1([CH3:38])[C@@H:30]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[O:29][P:27]([OH:37])(=[O:28])[O:26][CH2:25]1>C(Cl)Cl.CC(O)C>[OH:37][P:27]1(=[O:28])[O:29][C@@H:30]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:24]([CH3:23])([CH3:38])[CH2:25][O:26]1.[Br:1][C:2]1[C:21]([F:22])=[CH:20][C:5]2[O:6][C:7]3[CH:19]=[CH:18][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

5

Reactant 2

HCID 9829482(4R)-2-Hydroxy-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinan 2-oxideHCID 67358773(-)-(cis)-7-bromo-8-fluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-amine

Product 1

HCID 67359988(-)-(cis)-7-bromo-8-fluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-amine (4S)-2-hydroxy-5,5-dimethyl-4-phenyl-1,3,2-dioxaphosphorinane 2-oxideYield 79.4%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
86 °C

Procedure

To a solution of (±)-(cis)-7-bromo-8-fluoro-1,3,4,14b-tetrahydro-2H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-amine (18.58 g, 51.18 mmol) in 300 mL of CH2Cl2 and 60 mL of 2-propanol at 50° C. was added a warm solution of (+)-phencyphos (6.19, 25.59 mmol) in CH2Cl2 (300 mL) and 2-propanol (75 mL). The mixture was heated at 86° C. About 500 mL of CH2Cl2 was removed by careful evaporation, and 310 mL of 2-propanol was added; the mixture was then further concentrated until a final weight of ca. 250 g, and then gradually cooled down to 35° C. After 1 h, the formed crystals were collected by filtration, washed with 2-propanol and dried to yield 12.7 g of crude product (e.e. =95%). This compound was further recrystallized from methanol:CH2Cl2:2-propanol (7:5:2) to give the title compound (12.3 g, 39%, e.e.=99.8%).

Workup

  1. customAbout 500 mL of CH2Cl2 was removed by careful evaporation, and 310 mL of 2-propanol
  2. additionwas added
  3. concentrationthe mixture was then further concentrated until a final weight of ca. 250 g
  4. temperaturegradually cooled down to 35° C
  5. filtrationthe formed crystals were collected by filtration
  6. washwashed with 2-propanol
  7. customdried
  8. customto yield 12.7 g of crude product (e.e. =95%)
  9. customThis compound was further recrystallized from methanol:CH2Cl2:2-propanol (7:5:2)

Sources & evidence

ORD record
ord-77621fa1570d48c9b74d6b0528bee005
Source dataset
uspto-grants-2011_08
Patent number
US07989442B2

Reaction notes

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