Sodium borohydride → HCID 86586508, compound

HRID 1350146Notes

Reaction equation

HRID 1350146 reaction equation
[CH2:1]([C@@H:3]1[CH2:24][O:23][C:6]2=[C:7]3[C:12](=[CH:13][CH:14]=[C:5]2[NH:4]1)[N:11]=[C:10]([O:15][CH:16]([CH3:18])[CH3:17])[CH:9]=[C:8]3[C:19]([F:22])([F:21])[F:20])[CH3:2].[BH4-].[Na+]>FC(F)C(O)=O>[F:20][CH:19]([F:21])[CH2:8][N:4]1[C:5]2[C:6](=[C:7]3[C:12](=[CH:13][CH:14]=2)[N:11]=[C:10]([O:15][CH:16]([CH3:18])[CH3:17])[CH:9]=[C:8]3[C:19]([F:21])([F:22])[F:20])[O:23][CH2:24][C@H:3]1[CH2:1][CH3:2]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 69319657HCID 69319657, compound

Product 1

HCID 86586508HCID 86586508, compoundYield 98.9%

Reagents, catalysts & solvents 1

HCID 9788Difluoroacetic acidSolvent

Procedure

Compound 112 was prepared according to General Method 6 (EXAMPLE 3) from (3R)-3-ethyl-3,4-dihydro-8-isopropoxy-10-(trifluoromethyl)-2H-[1,4]oxazino[2,3-f]quinoline (13 mg, 0.04 mmol) and NaBH4 pellets (large excess, >10 equiv) in 3 mL difluoroacetic acid (0.01 M) stirred at rt for 12 h, to afford 8 mg (53%) of (3R)-4-(2,2-difluoroethyl)-3-ethyl-3,4-dihydro-8-isopropoxy-10-(trifluoromethyl)-2H-[1,4]oxazino[2,3-f]quinoline. This material (8 mg, 0.02 mmol) was carried on according to General Method 4 (EXAMPLE 1) by treatment with 1.5 mL acetic acid and 1.5 mL concentrated HCl and heated at 90° C. for 4 h to afford 4 mg (57%) of Compound 112, after purification by column chromatography (3:1 hexanes: EtOAc to 1:1 hexanes:EtOAc, gradient elution). 1H NMR (500 MHz, CDCl3) 12.19 (bs, 1H), 7.14 (s, 1H), 7.09 (d, 1H, J=8.8), 6.99 (d, 1H, J=9.3), 5.95 (m, 1H), 4.34 (dd, 1H, J=10.7, 1.5), 3.98 (dd, 1H, J=10.7, 2.4), 3.70 (m, 1H), 3.58 (m, 1H), 3.25 (m, 1H), 1.58 (m, 2H), 0.98 (t, 3H, J=7.3).

Sources & evidence

ORD record
ord-e540bb9b433844abaac1dfaa80f44e91
Source dataset
uspto-grants-2007_05
Patent number
US07214690B2

Reaction notes

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