4-(Bromomethyl)-1,2-difluorobenzene → (r)-2-[4-(3,4-Difluoro-benzyloxy)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 750037Notes

Reaction equation

HRID 750037 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][C:30]=1[F:31])[CH2:26]Br>>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:26][C:25]2[CH:28]=[CH:29][C:30]([F:31])=[C:23]([F:22])[CH:24]=2)=[CH:17][CH:16]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

3

Reactant 2

HCID 5814364-(Bromomethyl)-1,2-difluorobenzeneHCID 68999591(R)-2-(4-Hydroxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68997307(r)-2-[4-(3,4-Difluoro-benzyloxy)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 57.2%

Procedure

Followed the same procedure as that of step 2 in Example 91 with the use of (R)-2-(4-hydroxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (150 mg, 0.5 mmol) and 3,4-difluoro-benzyl bromide (145 mg, 0.6 mmol) to afford the title product, (120 mg, 55% yield); LCMS, 100% APCI+, Calcd; 419.5. Found m/z: 421.4 (M+2). 1H NMR (400 MHz, CDCl3); δ 1.47 (s, 9H), 1.80-2.09 (m, 4H), 3.28-3.46 (m, 2H), 3.69-3.91 (m, 1H), 4.02-4.18 (m 2H), 4.95 (s, 2H), 6.84-6.88 (m, 4H), 7.55-7.28 (m, 3H).

Sources & evidence

ORD record
ord-683a2e269adc4318979111668d5ae067
Source dataset
uspto-grants-2008_07
Patent number
US07402684B2

Reaction notes

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