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

HRID 331129Notes

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 B5.1) (6.85 g, 16.6 mmol) in toluene (205 ml) at 23° C. was added dropwise 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 a saturated solution of sodium hydrogencarbonate, extracted with ethyl acetate, washed organic layer with brine, dried over sodium sulphate, filtered off and evaporated totally. Dried at 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: m/z=366.2 [(M+H)+] and 368.1 [(M+2+H)+].

Workup

extractionextracted with ethyl acetate
washwashed organic layer with brine
dry with materialdried over sodium sulphate
filtrationfiltered off
customevaporated totally
customDried at high vacuum

Sources & evidence

ORD record: ord-6020c911733c4de2b055a63fcba9f394
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877744B2

Reaction notes

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