Sodium Bicarbonate → (R)-5-(5-bromo-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepan-3-one

HRID 403235Notes

Reaction equation

[NH2:1][C@@:2]([C:17]1[CH:22]=[C:21]([Br:23])[CH:20]=[CH:19][C:18]=1[F:24])([CH3:16])[C:3]([F:15])([F:14])[C:4]([CH3:13])([O:6][CH2:7][C:8](OCC)=[O:9])[CH3:5].C[Al](C)C.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[Br:23][C:21]1[CH:20]=[CH:19][C:18]([F:24])=[C:17]([C@:2]2([CH3:16])[C:3]([F:15])([F:14])[C:4]([CH3:13])([CH3:5])[O:6][CH2:7][C:8](=[O:9])[NH:1]2)[CH:22]=1

Participants

Conditions

Temperature: 23 °C

Procedure

To a solution of (R)-ethyl 2-(4-amino-4-(5-bromo-2-fluorophenyl)-3,3-difluoro-2-methylpentan-2-yloxy)acetate (intermediate A27A) (6.85 g, 16.6 mmol) in toluene (205 ml) at 23° C. was dropwise added trimethylaluminum (2 M in toluene, 10.8 ml, 21.6 mmol) and the light yellow solution was stirred at 23° C. for 2 h. Poured into sat. NaHCO3-sol., extracted with ethyl acetate, washed organic layer with brine, dried over Na2SO4, filtered off and evaporated totally, dried in high vacuum to give the (R)-5-(5-bromo-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepan-3-one (5.95 g, 16.2 mmol, 97.8% yield) as a light yellow solid, which was used without further purification. MS (ISP): m/z=366.2 [(M+H)+] and 368.1 [(M+2+H)+].

Workup

customat 23° C.
extraction, extracted with ethyl acetate
washwashed organic layer with brine
dry with materialdried over Na2SO4
filtrationfiltered off
customevaporated totally
customdried in high vacuum

Sources & evidence

ORD record: ord-f7fe4d8f5f2f46f0a167183a0942b9e5
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08748418B2

Reaction notes

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