Sodium triacetoxyborohydride → HCID 57236775, compound

HRID 1386770Notes

Reaction equation

HRID 1386770 reaction equation
[CH:1]([C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][N:5]([C@H:14]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[O:16])[CH2:4]1)=O.[F:33][C:34]([F:49])([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[CH2:35][CH2:36][CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.CCOC(C)=O>[CH3:26][O:25][C:22]1[CH:23]=[CH:24][C:19]([CH2:18][O:17][C:15](=[O:16])[C@H:14]([N:5]2[CH2:6][C@H:7]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C@@H:3]([CH2:1][N:40]3[CH2:41][CH2:42][CH:37]([CH2:36][CH2:35][C:34]([F:33])([F:49])[C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[CH2:38][CH2:39]3)[CH2:4]2)[CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]2)=[CH:20][CH:21]=1

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 18187489HCID 18187489, compoundHCID 53654320alpha-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-cyclohexaneacetic acid 4-methoxybenzyl ester

Product 1

HCID 57236775HCID 57236775, compoundYield 66.2%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Molecular sieve pellets (3 A) were added to a solution of 2-(R)-(3-(R)-formyl-4-(S)-phenylpyrrolidin-1-yl)-2-(cyclohexyl)acetic acid (4-methoxy)benzyl ester (34 mg, 0.078 mmol, from EXAMPLE 33, Step E) and 4-(3,3-difluoro-3-phenylpropyl)piperidine (20 mg. 0.084 mmol, from EXAMPLE 154, Step D) in 1,2-dichloroethane (0.75 mL). The mixture was stirred for 45 min. at RT before the addition of sodium triacetoxyborohydride (19.9 mg, 0.094 mmol). After 4 h, the mixture was diluted with EtOAc (20 mL) and washed with saturated aq. NaHCO3 (10 mL) followed by saturated aq. NaCl (10 mL). The organic layer was dried (Na2SO4), decanted, and evaporated. Purification by flash column chromatography on silica gel, eluting with 92:8 v/v, then 86:14 v/v hexanes/EtOAc, gave 34 mg of the title compound as a colorless film. 1H NMR (400 MHz, CD3OD) δ 7.47-7.40 (m, 5H), 7.36 (d, J=8,22H), 7.23 (t, J=7, 2H), 7.15 (t, J=7, 1H), 7.10 (d, J=7, 1H), 6.90 (d, J=8, 2H), 5.12 (s, 2H), 3.18 (dd, J=9, 7, 1H), 3.12-3.06 (m, 2H), 2.80-2.56 (m, 4H), 2.51 (dd, J=9, 7, 11H), 2.30-2.19 (m, 3H), 2.12 (tm, J=16, 2H), 1.94 (bd, J=12, 1H), 1.86-1.50 (m, 9H), 1.31-0.89 (m, 10H); ESI-MS 659 (M+H).

Workup

  1. washwashed with saturated aq. NaHCO3 (10 mL)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. customdecanted
  4. customevaporated
  5. customPurification by flash column chromatography on silica gel
  6. washeluting with 92:8 v/v

Sources & evidence

ORD record
ord-83ca68badd0240929325fc96d4d7250e
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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