Sodium Hydroxide → HCID 89733983, compound

HRID 926370Notes

Reaction equation

[C:1]1([C@H:7]([NH:10][C:11]([C:13]2[CH:14]=[CH:15][N:16]3[C:21]=2[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:12])[CH2:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:22]N1C(=O)CCC1=O.[OH-].[Na+]>ClCCl>[C:1]1([C@H:7]([NH:10][C:11]([C:13]2[CH:14]=[C:15]([Br:22])[N:16]3[C:21]=2[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:12])[CH2:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 5,6,7,8-tetrahydro-indolizine-1-carboxylic acid ((R)-1-phenyl-propyl)-amide (9i) (9.7 g, 34.35 mmol) in dry dichloromethane (200 ml) at −78° C. was added N-bromo-succinimide (6.11 g, 34.35 mmol) in several portions (over 2 min) and the mixture was stirred for 1 h min at −78° C., 1 h at 0° C. and 30 min at 25° C. Then 500 ml aqueous 2% sodium hydroxide was added, and the mixture was extracted 3 times with dichloromethane, the combined organic layers were dried over sodium sulfate, evaporated and the crude product was purified by reverse phase HPLC (acetonitrile/water gradient with 0.1% trifluoroacetic acid) to give 5.24 g (42%) of 3-bromo-5,6,7,8-tetrahydro-indolizine-1-carboxylic acid ((R)-1-phenyl-propyl)-amide. LC/MS (method 4): Rt=1.33 min; m/z=361.21 (M+H+).

Workup

custom1 h
customat 0° C.
custom30 min
customat 25° C
extractionthe mixture was extracted 3 times with dichloromethane
dry with materialthe combined organic layers were dried over sodium sulfate
customevaporated
customthe crude product was purified by reverse phase HPLC (acetonitrile/water gradient with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record: ord-82a7cd44f09648a6984c29e728315324
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284333B2

Reaction notes

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